Combined Effects of Cd and Hg on Liver and Kidney Histology and Function in Wistar Rats

The present study was performed in order to discern the effects of combined exposure to cadmium and mercury on liver function and histopathological alterations in male adult Wistar rats. In the present investigation, cadmium (100 mg/l) and mercury (25 mg/l) were administered orally for 10 weeks separately or in combination. The rational for studying cadmium and mercury is that both of these metals are encountered frequently in the same contaminated areas. In liver, the activities of serum alanine aminotransferase (ALT) and aspartate amino tranferase (AST) increased significantly in the cadmium (Cd) and mercury (Hg) alone or in combination (Cd + Hg) compared to the control suggesting that both cadmium and mercury cause hepatotoxicity spatially when co-administrated. We noted an increase in serum lactate dehydrogenase (LDH) activity in Cd and combined Cd + Hg treated groups while it decreased in Hg treated group. There was no statistically significant change in the level of total bilirubilin. Serum urea concentration showed a significant increase in the Cd and Hg groups compared to the control group. However an increase in serum creatinine concentration was noted only in the combined treated rats showing that renal insufficiency is more serious in the co-exposed group. Light microscopic examination indicated severe histological changes in the two organs under Cd and mercury influence. Results of the present investigation clearly showed that mercury has profound effects of hepatic handling of cadmium (synergistic effect) as shown by histological and biochemical results. Moreover, we observed a antagonist effect between these two toxic metals on kidney markers such as urea.

Long-Term Impact of Acute Retinoic Acid Supplementation at the Young Age on Testicular Architecture of Wistar Albino Rats

Introduction: Inappropriate and excess vitamin supplementation, particularly for vitamin A, is increasingly recognized as a public health problem in developed countries. On the other hand, blind supplementation of vitamin A, for children in developing countries is a subject of controversy in the literature. The crucial role of vitamin A in the process of spermatogenesis in adult rodents is well established, but only a few publications are consecrated to the long-term effect of vitamin A intake at a young age on testicular development and differentiation. Objectives: Our study aimed to evaluate the long-term effects of acute supplementation at an early age, in the post-natal period, on spermatogenesis and testicular trophicity at adult age. Material and Methods: Young Wistar Albinos rats of 22 days received an acute high dose of supplementation of vitamin A (retinyl palmitate). The control group, group 1, received only extra virgin olive oil, Group 2 a dose of 7000 IU/kg of retinyl palmitate, group 3, 14,000 IU/kg, and Group 4 a dose of 28,000 IU/kg. At 10 weeks of age, the testes’ testosterone levels were measured by ELISA. For histological assessment, sections were stained with Hematoxylin eosin, and the Johnsen score was used to evaluate spermatogenesis in the seminiferous tubules. Results: The average testicular weights of rats were significantly lower in group 4 (p < 0.05), and so was the testosterone level in the testis compared to the control group (p .01). Most of the seminiferous tubules were concerned by an arrest of spermatogenesis and the Johnsen score was decreased with a mean score of 5.96 ± 1.60 (p .001) in that Group. In Group 3, Johnsen’s score was significantly better than the one obtained with the control. Conclusion: We observed a negative effect in the long term with a high acute dose of supplementation of retinyl palmitate at a young age, on testicular development and differentiation. Despite a return to normal diet after that supplementation, during childhood, impaired spermatogenesis was identified at the adult age with an arrest of spermatogenesis. The reversibility of that lack of differentiation by a return to a normal diet is questionable and would need more investigation.

Histopathology of nonalcoholic fatty liver disease

Histological analysis of liver biopsies remains a standard against which other methods of assessment for the presence and amount of hepatic injury due to nonalcoholic fatty liver disease(NAFLD) are measured.Histological evaluation remains the sole method of distinguishing steatosis from advanced forms of NAFLD,i.e.nonalcoholic steatohepatitis(NASH) and fibrosis.Included in the lesions of NAFLD are steatosis,lobular and portal inflammation,hepatocyte injury in the forms of ballooning and apoptosis,and fibrosis.However,patterns of these lesions are as distinguishing as the lesions themselves.Liver injury in adults and children due to NAFLD may have different histological patterns.In this review,the rationale for liver biopsy,as well as the histopathological lesions,the microscopically observable patterns of injury,and the differential diagnoses of NAFLD and NASH are discussed.

Liver histology in ICU patients dying from sepsis:A clinico-pathological study

AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.

Evaluation of the impact of leucocytospermia on semen oxidative status by chemiluminescence technique in infertile men

The presence of high reactive oxygen species (ROS) levels in semen is a major factor involved in the decline of male fertility. In seminal plasma, ROS are mainly produced by activated leucocytes. Spermatozoa were the first cell type reported to show a potential susceptibility to oxidative damage. The aim of our study was to evaluate the impact of leucocytospermia on basal and FMLP (Formyl-Methionyl-Leucyl-Phenylalanine) induced oxidative status in semen of infertile men. We also analyzed the correlations of the spermatic parameters with amounts of ROS in semen. Our study included 50 semen samples of infertile men. Sperm analysis was performed using WHO standardized method. Seminal leucocytes were quantified using peroxidase technique. The measurement of ROS levels in semen was made by chemiluminescence assay. We measure respectively ROS amounts in neat semen and in washed sperm cells suspension from the same ejaculate. We also applied the test of provocation of leucocytes by FMLP on neat and washed samples to assess the spermatic oxidative status after leucocyte stimulation. Our results showed significant correlations between ROS levels in neat semen and many sperm parameters: motility, sperm concentration, leucocytes concentration and the rate of sperm cytoplasmic droplets. The studied samples were divided into 2 groups: (G1) composed of 36 samples without leucocytospermia and (G2) composed of 14 leucospermic samples. ROS levels were significantly lower in G1 than in G2 (p = 0.002). ROS production was significantly increased after application of FMLP in washed leucospermic samples (p = 0.001). The measurement of ROS in neat semen is a considerable contribution to explore the impairment of semen quality in infertile men. ROS levels in washed semen reflect the oxidative status generated by sperm preparation techniques used in assisted reproductive procedures. Levels of ROS are highly influenced by the presence of leucocytes and associated with decreased seminal parameters.

Anti-inflammatory and analgesic properties of Moroccan medicinal plants:Phytochemistry,in vitro and in vivo investigations,mechanism insights,clinical evidences and perspectives

Moroccan medicinal plants exhibit several pharmacological properties such as antimicrobial,anticancer,antidiabetic,analgesic,and anti-inflammatory effects,which are related to the presence of numerous bioactive compounds,including phenolic acids,flavonoids,and terpenoids.In the present review,we systematically evaluate previously published reports on the anti-inflammatory and analgesic effects of Moroccan medicinal plants.The in vitro investigations revealed that Moroccan medicinal plants inhibit several enzymes related to inflammatory processes,whereas in vivo studies noted significant anti-inflammatory and analgesic effects as demonstrated using different experimental models.Various bioactive compounds exhibiting in vitro and in vivo anti-inflammatory and analgesic effects,with diverse mechanisms of action,have been identified.Some plants and their bioactive compounds reveal specific secondary metabolites that possess important anti-inflammatory effects in clinical investigations.Our review proposes the potential applications of Moroccan medicinal plants as sources of anti-inflammatory and analgesic agents.

Spontaneous pancreatic undifferentiated pleomorphic sarcoma in a laboratory rat: A case report

We present a case of spontaneous undifferentiated/unclassified sarcoma,of a pleomorphic subtype formerly known as malignant fibrous histiocytoma(UPS/MFH),arising from the pancreas of a laboratory rat.The mass was excised after laparotomy from a 6‐month‐old female laboratory Wistar rat.It presented a giant multilobulated mass of irregular shape,which had arisen from the pancreas and occupied almost the entire peritoneal cavity.Histologically the tumor was characterized by a highly variable morphological pattern,with frequent transitions from storiform to pleomorphic areas.An extensive immunohistochemical examination revealed no specific lines of differentiation.Immunohistochemical positivity was observed only to MIB‐1(high Ki‐67 proliferation index),vimentin and CD68 antibodies.The diagnosis was compatible with UPS/MFH.To the best of our knowledge,the present case is the first report of a spontaneous primary UPS/MFH arising from the pancreas of a laboratory rat.

Peripapillary intrachoroidal cavitation at the crossroads of peripapillary myopic changes

AIM:To analyze the prevalence of peripapillary intrachoroidal cavitation(PICC)in eyes with gamma peripapillary atrophy(γPPA),in eyes with peripapillary staphyloma(PPS)and in those combiningγPPA and PPS and to analyze border tissue discontinuity in PICC.METHODS:This prospective cross-sectional non interventional study included highly myopic eyes.Non-highly myopic eyes were used as control.Radial and linear scans centered on the optic nerve head were performed using spectral-domain optical coherence tomography.Variables were analyzed along the twelve hourly optical coherence tomography sections in both eyes of each subject.RESULTS:A total of 667 eyes of 334 subjects were included:229(34.3%)highly myopic eyes and 438(65.7%)non highly myopic eyes.The mean age of the highly myopic group was 48.99±17.81y.PICC was found in a total of 40 eyes and in 13.2%(29/220)of highly myopic eyes.PICC was found in 10.4%(40/386)of eyes withγPPA,in 20.5%(40/195)of eyes with PPS and in 22.7%(40/176)of those combiningγPPA and PPS.All the eyes with PICC showed the co-existence ofγPPA and PPS whereas none of the eyes presenting only one of these entities exhibited PICC.A border tissue discontinuity in theγPPA area was found in all eyes with PICC.CONCLUSION:We confirm the presence of a border tissue discontinuity in theγPPA area of all eyes with PICC.These findings suggest the involvement of mechanical factors in the pathogenesis of PICC which may contribute to PICC-related visual field defects.

Changes of the intestinal endocrine cells in the C57BL/6 mouse after implantation of murine lung carcinoma (3LL): An immunohistochemical quantitative study

AIM: To study the distributions and frequencies of intestinal endocrine cells in the C57BL/6 mouse with immunohistochemical method using seven types of specific antisera against chromogranin A (CGA), serotonin,somatostatin, glucagons, gastrin, cholecystokinin (CCK)-8 and human pancreatic polypeptide (hPP) after abdominal subcutaneous implantation of murine lung carcinoma (3LL).METHODS: The experimental animals were divided into two groups, one is non-implanted Sham and the other is 3LL-implanted group. Samples were collected from six regions of intestinal tract at 28th d after implantation of 3LL cells (1×105 cell/mouse).RESULTS: In this study, five types of immunoreactive (IR) cells were identified except for gastrin and hPP. The regional distributions of the intestinal endocrine cells in the 3LL-implanted group were similar to those of the non-implanted Sham. However, significant decreases of IR cells were detected in 3LL-implanted group compared to those of non-implanted Sham. CGA- and serotonin-IR cells significantly decreased in 3LL-implanted groups compared to that of non-implanted Sham. Somatostatin-IR cells in the jejunum and ileum and CCK-8-IR cells in the jejunum of 3LL-implanted groups significantly decreased compared to that of non-implanted Sham. In addition,glucagon-IR cells were restricted to the ileum and colon of non-implanted Sham.CONCLUSION: Implantation of tumor cell mass (3LL)induced severe quantifiable changes of intestinal endocrine cell density and the abnormality in density of intestinal endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

A comparative pattern of lectin-binding in the endometrial glands of the uterus and placenta of healthy buffaloes and bovines at early gestation

Water buffalo(Bubalus bubalis)and domestic cattle(Bos taurus)are closely related species.However,embryo transfer interspecies has been attempted without any success.The failure in hybrid embryo-implantation is associated with the glycocode in the maternal-fetal interface.Glycosylation patterns have been studied in different species of ruminants;however,in B.bubalis,only the binucleated cells(BNC)have been analyzed.This glycocode is essential for a successful embryo-implantation and can be defined by Lectin-Histochemistry(LHC).The aim of this study is to compare the glycosylation pattern of placenta and uterus in water buffaloes and cattle by LHC.Tissue samples of placenta and uterus from pregnant Mediterranean female water buffaloes(Buf1)and Angus cows(Bov1)were analyzed.All animals were euthanized at 98 days of gestation.LHC was carried out using twelve lectins(Con A,LCA,PSA,sWGA,PHA-e,SBA,UEA-1,WGA,RCA-1,PNA,DBA,BSA-1).The intensity of lectin binding was semiquantitatively scored using a scale of 0(negative)to 3(strongly positive).Difference between species was found in trophoblast layer by PSA,SWGA,PNA and BSA-1,in BNC,and in the mononuclear cells by LCA,PSA,PHA-e,DBA,BSA-1,PNA.In utero,differences in the apical cellular membrane and the secretion of glands were identified by DBA and RCA-1,and in the cytoplasm of those glandular epithelial cells by PHA-e,BSA-1,WGA,and SBA.In both species,BNC presented a strong positive reaction with DBA and SBA,a moderate response by LCA,PHA-e,BSA-1 and PNA lectin,and a low reaction by PSA,UEA-1,SWGA,WGA,Con A and RCA-1.The results found in this study suggest that although both species are closely related,glycosylation patterns in the placenta and uterus are different,thus providing a possible reason for embryo transfer not being possible between these species.

Genetics of congenital anomalies of the hand

Congenital anomalies of the hand are malformations occurring during the development of the human limb,and present as isolated disorders or as a part of a syndrome.During the last years,molecular analysis techniques have offered increasing knowledge about the molecular basis of hand malformations.Disturbances in the signaling pathways during the development of the upper limb result in malformations of the upper extremity.At present,several genes have been identified as responsible for hand anomalies and other have been recognized as suspect genes related to them.Different and new high throughput methods have been introduced for the identification of the gene mutations.In the current editorial,we summarize concisely the current molecular status of isolated hand genetic disorders and the recent progress in molecular genetics,including the genes related to the disorder.This progress improves the knowledge of these disorders and has implications on genetic counselling and prenatal diagnosis.

Action of the Disintegrin Contortrostatin on Breast Cancer Cell Primary Cultures

Integrins mediate cell adhesion to the extracellular matrix (ECM). In particular, integrin alphavbeta3 recognizes the RGD motif as a ligand-binding site on various extracellular molecules of the extracellular matrix. Integrin aphavbeta3 has been associated with high malignant potential in breast cancer cells, and has signalized the onset of widespread metastasis. In recent years, several antagonists of integrin alphavbeta3, including snake venom disintegrins, have been used as potential anti-cancer agents. In the present work, the effect of contortrostatin, a disintegrin isolated from the venom of the snake Agkistrodon contortrix, was studied on primary cultures of human breast cancer cell. Scanning and transmission electron microscopy were employed in order to examine alterations in cell morphology and fluorescent microscopy and visualize changes in distribution of integrin alphavbeta3 and talin. Fluorescent localization of caspase 8 was made in order to visualize any sign of proapoptotosis and western immunoblotting of integrin, talin and annexin was undertaken in order to identify changes. The results suggest that the snake venom contortrostatin seriously affects cell morphology, adhesion and mobility and induces breast cancer cells to apoptosis.

Assessment of Spermatic Chromatin Decondensation by the Toluidine Blue Assay in Infertile Patients in Cotonou

Background: A high level of sperm chromatin decondensation results in loss of DNA quality and it is associated with poor embryonic prognosis in Assisted Reproductive Technology (ART). This had lead to introduction of sperm DNA compaction testing in assessment of clinical male infertility. Toluidine blue assay is one of most commonly used tests to measure chromatin decondensation in research studies and also in clinical routine use. So the objective of our study was to assess the level of sperm chromatin decondensation by toluidine blue assay in men dealing with couple infertility. Methods: The sperm samples of 96 patients referred for infertility, over a 4-month period from September 2020 to January 2021, were stained with toluidine blue and observed under an optical microscope. These were evaluated according to the World Health Organization. Results: The 25 - 34 age group was the most represented among infertile men. There was a non-significant correlation between age and the level of spermatic chromatin condensation (r = 0.0348). Spermatic parameters had averages above standards norms, apart from that of low vitality. Spermatic chromatin decondenization affected 96% of infertile patients. Asthenozoospermia was the most common abnormality. Among standard parameters of spermogram, only the concentration of spermatozoa in the semen was weakly correlated (r = 0.18) with sperm chromatin decondensation. Conclusion: The level of sperm chromatin condensation is, on the one hand, a parameter independent of the age of the subject; on the other hand, allows to evaluate male infertility, like the classic parameters of the spermogram and spermocytogram. However, in view of the high probability of changes in the nuclear quality of sperm intrinsic to the analysis process and sperm concentration, an improvement of the toluidine blue test using the swim-up technique and associated with image processing software is possible.

Serum leptin and ghrelin in chronic hepatitis C patients with steatosis

AIM:To determine the associations between leptin and ghrelin concentrations and sustained virological response(SVR)in chronic hepatitis C patients with ste-atosis.METHODS:We retrospectively assessed 56 patients infected with hepatitis C virus(HCV)genotype-1 and 40 with HCV genotype-3.Patients with decompensated cirrhosis,and those with other causes of chronic liver disease,were excluded.Serum HCV-RNA concentra-tions were measured before the initiation of treatment;at weeks 12(for genotype 1 patients),24 and 48 during treatment;and 24 wk after the end of treatment.Genotype was determined using INNO-LIPA HCV as-says,and serum leptin and ghrelin concentrations were measured using enzyme-linked immunosorbent assay.Biopsy specimens were scored according to the Ishak system and steatosis was graded as mild,moderate,or severe,according to the Brunt classif ication.RESULTS:Overall,SVR was positively related to the presence of genotype-3,to biopsy-determined lower histological stage of liver disease,and lower grade of steatosis.Patients ≥ 40 years old tended to be less responsive to therapy.In genotype-1 infected pa-tients,SVR was associated with a lower grade of liver steatosis,milder fibrosis,and an absence of insulin resistance.Genotype-1 infected patients who did not achieve SVR had significantly higher leptin concen-trations at baseline,with significant increases as the severity of steatosis worsened,whereas those who achieved SVR had higher ghrelin concentrations.In genotype-3 infected patients,SVR was associated only with fibrosis stage and lower homeostasis model as-sessment insulin resistance at baseline,but not with the degree of steatosis or leptin concentrations.Geno-type-3 infected patients who achieved SVR showed signif icant decreases in ghrelin concentration at end of treatment.Baseline ghrelin concentrations were elevat-ed in responders of both genotypes who had moderate and severe steatosis.CONCLUSION:Increased serum leptin before treat-ment may predict non-SVR,especially in HCV geno-type-1 infected patients,whereas increased ghrelin may predict SVR in genotype-1.

Sperm quality improvement after date seed oil in Vitro supplementation in spontaneous and induced oxidative stress

In vitro supplementation with date seed oil （DSO） can protect spermatozoa against hydrogen peroxide （HiO2）- mediated damage and can improve sperm function, possibly owing to antioxidant properties. We tested the antioxidant effects of DSO on human sperm motility, sperm viability, reacted acrosome and lipid peroxidation assessed in vitro after H202-mediated oxidative damage in spermatozoa. Sixteen patients （mean age： 35 years; range： 25-45 years） referred to the Histology-Embryology Laboratory of the Medicine Faculty of Sfax for semen analysis after 12-24 months of sexual intercourse without conception were selected. After spermiogram, sperm selection by twointerface discontinuous Sill Select gradient was performed, and selected spermatozoa were used in four experimental assays： control; incubation with 100um H2O2; incubation with 0.1% DSO; and co-incubation with 0.1% DSO and 100 um H2O2. Motility and viability were determined using World Health Organization criteria. Acrosome reaction and lipid peroxidation were assessed by staining with fluorescein isothiocyanate-Pisum sativum and spectrophotometric measurement of malondialdehyde, respectively. Results showed that incubation with H2O2 alone led to a significant increase in lipid peroxidation （57.83%, P 〈 0.05） associated with a significant decrease in sperm motility, sperm viability （after 30 min and 24 h） and percentage of reacted acrosome （P 〈 0.05）. Date seed oil im- proved sperm motility after 24 h of incubation （P 〈 0.05） and protected spermatozoa against the deleterious effects of H2O2 on motility, viability, acrosome reaction and lipid peroxidation. We conclude that supplementation with DSO may have a function in antioxidant protection against male infertility.

A silybin-phospholipids complex counteracts rat fatty liver degeneration and mitochondrial oxidative changes

AIM:To investigate the effectiveness of antioxidant compounds in modulating mitochondrial oxidative alterations and lipids accumulation in fatty hepatocytes.METHODS:Silybin-phospholipid complex containing vitamin E(Realsil) was daily administered by gavage(one pouch diluted in 3 mL of water and containing 15 mg vitamin E and 47 mg silybin complexed with phospholipids) to rats fed a choline-deprived(CD) or a high fat diet [20% fat,containing 71% total calories as fat,11% as carbohydrate,and 18% as protein,high fat diet(HFD)] for 30 d and 60 d,respectively.The control group was fed a normal semi-purified diet containing adequate levels of choline(35% total calories as fat,47% as carbohydrate,and 18% as protein).Circulating and hepatic redox active and nitrogen regulating molecules(thioredoxin,glutathione,glutathione peroxidase),NO metabolites(nitrosothiols,nitrotyrosine),lipid peroxides [malondialdehyde-thiobarbituric(MDA-TBA)],and pro-inflammatory keratins(K-18) were measured on days 0,7,14,30,and 60.Mitochondrial respiratory chain proteins and the extent of hepatic fatty infiltration were evaluated.RESULTS:Both diet regimens produced liver steatosis(50% and 25% of liver slices with CD and HFD,respectively) with no signs of necro-inflammation:fat infiltration ranged from large droplets at day 14 to disseminated and confluent vacuoles resulting in microvesicular steatosis at day 30(CD) and day 60(HFD).In plasma,thioredoxin and nitrosothiols were not significantly changed,while MDA-TBA,nitrotyrosine(from 6 ± 1 nmol/L to 14 ± 3 nmol/L day 30 CD,P < 0.001,and 12 ± 2 nmol/L day 60 HFD,P < 0.001),and K-18(from 198 ± 20 to 289 ± 21 U/L day 30 CD,P < 0.001,and 242 ± 23 U/L day 60 HFD,P < 0.001) levels increased significantly with ongoing steatosis.In the liver,glutathione was decreased(from 34.0 ± 1.3 to 25.3 ± 1.2 nmol/mg prot day 30 CD,P < 0.001,and 22.4 ± 2.4 nmol/mg prot day 60 HFD,P < 0.001),while thioredoxin and glutathione peroxidase were initially increased and then decreased.Nitrosothiols were constantly increased.MDA-TBA levels were five-fold increased from 9.1 ± 1.2 nmol/g to 75.6 ± 5.4 nmol/g on day 30,P < 0.001(CD) and doubled with HFD on day 60.Realsil administration significantly lowered the extent of fat infiltration,maintained liver glutathione levels during the first half period,and halved its decrease during the second half.Also,Realsil modulated thioredoxin changes and the production of NO derivatives and significantly lowered MDA-TBA levels both in liver(from 73.6 ± 5.4 to 57.2 ± 6.3 nmol/g day 30 CD,P < 0.01 and from 27.3 ± 2.1 nmol/g to 20.5 ± 2.2 nmol/g day 60 HFD,P < 0.01) and in plasma.Changes in mitochondrial respiratory complexes were also attenuated by Realsil in HFD rats with a major protective effect on Complex Ⅱ subunit CII-30.CONCLUSION:Realsil administration effectively contrasts hepatocyte fat deposition,NO derivatives formation,and mitochondrial alterations,allowing the liver to maintain a better glutathione and thioredoxin antioxidant activity.

Polydactyly:Clinical and molecular manifestations

Polydactyly is a malformation during the development of the human limb,which is characterized by the presence of more than the normal number of fingers or toes.It is considered to be one of the most common inherited hand disorders.It can be divided into two major groups:Non-syndromic polydactyly or syndromic polydactyly.According to the anatomical location of the duplicated digits,polydactyly can be generally subdivided into pre-,post-axial,and mesoaxial forms.Non-syndromic polydactyly is often inherited with an autosomal dominant trait and defects during the procedure of anterior-posterior patterning of limb development are incriminated for the final phenotype of the malformation.There are several forms of polydactyly,including hand and foot extra digit manifestations.The deformity affects upper limbs with a higher frequency than the lower,and the left foot is more often involved than the right.The treatment is always surgical.Since the clinical presentation is highly diverse,the treatment combines single or multiple surgical operations,depending on the type of polydactyly.The research attention that congenital limb deformities have recently attracted has resulted in broadening the list of isolated gene mutations associated with the disorders.Next generation sequencing technologies have contributed to the correlation of phenotype and genetic profile of the multiple polydactyly manifestations and have helped in early diagnosis and screening of most nonsyndromic and syndromic disorders.

AMACR is associated with advanced pathologic risk factors in sporadic colorectal adenomas

AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorectal adenomas.METHODS: Fifty-f ive cases of sporadic colorectal adenomas were categorized according to the Vienna classif ication for Gastrointestinal Neoplasia.These corresponded to a total of 98 different intra-lesion microscopic f ields that were further independently assigned a histological grade based on the old nomenclature (mild,moderate,severe dyplasia and carcinoma in situ).AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e.gender,age,localization,grade of dysplasia,size and conf iguration.RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years);37 patients were males and 18 were females.Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm),including 18 tubular,16 villous,20 mixed or tubulovillous,and 1 giant sessile villous adenoma.AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P = 0.002).Most adenomas exhibiting high grade dysplasia with in situ carcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%),(P = 0.005).In AMACR positive adenomas featuring severe dysplasia-like or in situ carcinoma-like areas,AMACR staining was not necessarily observed in the in situ component.Positivity in intra-lesion of mild,moderate or severe dysplasia-like foci was more often encountered in adenomas harboring in situ,intramucosal or inf iltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%),P < 0.001].Strong AMACR expression was found in 11 out of 17 villous adenomas,but in only 1 out of 18 tubular lesions (P = 0.005).Larger lesions,i.e.> 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%),P = 0.02].Overall,AMACR expression was associated with the grade of dysplasia,as well as with the size and conf iguration of adenomas,i.e.the consensus risk factors applied to colorectal adenoma patient surveillance.CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.

Liver Function and Structure in Rats Treated Simultaneously with Cadmium and Mercury

The effect of cadmium chloride (150 mg/l) and mercury (II) chloride (80 mg/l) either alone or in combination in drinking water for 4 weeks on function and structure of the liver of male rats was studied. Results indicated that the ratio of liver weight to body weight and the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase noted in rats co-exposed to cadmium and mercury were intermediate between those noted in the individually metal treated rats. The histopathological study showed that the individual metal and the combined metal treatments caused severe liver damage. The degree of these changes noted in rats co-exposed to cadmium and mercury was not higher than those signalized in individual treatment. The biochemical and the histological changes observed in rats co-exposed to cadmium and mercury show that there is not an additive effect between these two metals.

同时伴有Ⅰ级和Ⅲ级宫颈上皮内瘤样病变的患者宫颈人乳头样瘤病毒DNA的检测与分型:生物学发展还是独立性病变?

Objective: To examine the HPV type infection of cervical cone specimens with coexistent CIN1 and CIN3 lesions, in order to define if coexistence of low-and high-grade lesions in the same cervix represent different stages of evolution in a continuing process that is caused by a single viral type or independent lesions induced by different HPV types. Study design: The examined material included 43 cases with coexistent CIN1 and CIN3 in the cone biopsy specimen. Detection and typing of HPV was made by RFLP-PCR. Results: All CIN1 lesions were HPV positive, while three CIN3 lesions were HPV-negative. The proportion of agreement of the HPV type in the two lesions, excluding negative cases (n = 40), was 60% (95% confidence interval: 43.3-75.1). HPV 16 was the most common type in both CIN3 (56.8% ) and CIN1 (46.5% ). Conclusions: The so-called morphologic progression of CIN is not always synonymous with biologic progression, since many coexistent CIN lesions are caused by different HPV types, and so represent different cell clones. Clonality of coexistent CIN lesions may be implicated in the evolution of CIN as other recent studies have shown.