Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment.Serum creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function.Here,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney function.We used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 m2.We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum creatinine.The estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all equations.Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 m2.We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients.Therefore,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Increased alcohol consumption during the COVID-19 pandemic:A cross-sectional study

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic has significantly impacted health,mental well-being,and societal functioning,particularly for individuals with psychiatric conditions and substance use disorders.Recent evidence highlights a concerning increase in alcohol consumption during the pandemic,with a study spanning 2015-2020 indicating heightened usage,especially among young and middle-aged adults,for relaxation and tension relief.Additionally,addressing challenges exacerbated by the pandemic,another study underscored persistent barriers to healthcare access,resulting in increased alcohol and tobacco use rates and limited healthcare options.These findings shed light on the unique vulnerabilities exposed by the pandemic,emphasizing the need to investigate further its impact on alcohol consumption in diverse non-urban American communities.AIM To investigate the impact of the COVID-19 pandemic on alcohol abuse using socioeconomic and medical parameters in diverse non-urban community in America.METHODS Based on a cross-sectional analysis of 416 participants the United States in 2021,the study utilized The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition criteria to categorize alcohol consumption levels.Participants aged 21 years and above were surveyed through an online platform due to COVID-19 challenges.The survey was conducted from January 14 to January 31,2022,recruiting participants via social media and ensuring anonymity.Informed consent was secured,emphasizing the voluntary nature of participation,and participants could only take the survey once.RESULTS Out of 416 survey respondents,396 met eligibility criteria,with 62.9%reporting increased alcohol consumption during COVID-19.Males(68.8%)and ages 21-29 years(34.6%)predominated.Low alcohol consumption decreased by 2.8%(P=0.237),moderate by 21.4%(P<0.001),and heavy increased by 14.9%(P<0.001).Alcohol abuse rose by 6.5%(P=0.0439),with a 7%increase in self-identified alcohol abusers/alcoholics.Seeking treatment during COVID-19 rose by 6.9%.Easier alcohol access(76.0%)was reported,while 80.7%found it harder to access medical care for alcohol-related issues.These findings highlight the pandemic's impact on alcohol consumption and healthcare access,emphasizing the need for targeted interventions during public health crises.CONCLUSION The COVID-19 pandemic exacerbated alcoholism and abuse,with increased heavy consumption(P<0.001)and abuse(P=0.0439).Access to medical programs for addressing alcohol abuse declined,highlighting the need for targeted intervention.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

BACKGROUND Metabolic-dysfunction associated steatotic liver disease(MASLD)is a hepatic manifestation of metabolic syndrome.Studies suggest ornithine aspartate(LOLA)as drug therapy.AIM To analyze the influence of LOLA intake on gut microbiota using a nutritional model of MASLD.METHODS Adult male Sprague Dawley rats were randomized into three groups:Control(10 rats fed with a standard diet),MASLD(10 rats fed with a high-fat and choline-deficient diet),and LOLA(10 rats receiving 200 mg/kg/d LOLA,after the 16th week receiving high-fat and choline-deficient diet).After 28 wk of the experiment,animals were euthanized,and feces present in the intestine were collected.Following fecal DNA extraction,the V4 region of the 16S rRNA gene was amplified followed by sequencing in an Ion S5™system.RESULTS Alpha and beta diversity metrics were comparable between MASLD and LOLA.3 OTUs were differentially abundant between MASLD and LOLA,which belong to the species Helicobacter rodentium,Parabacteroides goldsteinii,and Parabacteroides distasonis.The functional prediction provided two different metabolic profiles between MASLD and LOLA.The 9 pathways differentially abundant in MASLD are related to a change in energy source,adenosine/purine nucleotides degradation as well as guanosine and adenosine deoxyribonucleotides biosynthesis.The 14 pathways differentially abundant in LOLA are associated with four major metabolic functions primarily influenced by L-aspartate,including tricarboxylic acid cycle pathways,purine/guanosine nucleotides biosynthesis,pyrimidine ribonucleotides biosynthesis and salvage as well as lipid IVA biosynthesis.CONCLUSION Although LOLA had no influence on alpha and beta diversity in this nutritional model of MASLD,it was associated with changes in specific gut microbes and their related metabolic pathways.

Associations of PNPLA3 and LEP genetic polymorphisms with metabolic-associated fatty liver disease in Thai people living with human immunodeficiency virus

BACKGROUND The prevalence of metabolic-associated fatty liver disease(MAFLD)is a growing public health issue in people living with human immunodeficiency virus(PLWH).However,the pathophysiology of MAFLD is still unknown,and the role of genetic variables is only now becoming evident.AIM To evaluate the associations of gene-polymorphism-related MAFLD in PLWH.METHODS The study employed transient elastography with a controlled attenuation parameter≥248 dB/m to identify MAFLD in patients from a Super Tertiary Hospital in central Thailand.Candidate single-nucleotide polymorphisms(SNPs)were genotyped using TaqMan®MGB probe 5'nuclease assays for seven MAFLD-related genes.Statistical analyses included SNP frequency analysis,Fisher's Exact and Chi-square tests,odds ratio calculations,and multivariable logistic regression.RESULTS The G-allele carriers of PNPLA3(rs738409)exhibited a two-fold rise in MAFLD,increasing by 2.5 times in MAFLD with human immunodeficiency virus infection.The clinical features and genetic patterns imply that LEP rs7799039 A-allele carriers had a nine times(P=0.001)more significant chance of developing aberrant triglyceride among PLWH.CONCLUSION The current study shows an association between PNPLA3 rs738409 and LEP rs7799039 with MAFLD in PLWH.

Bioactive Components of Chinese Herbal Medicines in the Treatment of Glucose and Lipid Metabolism Disorders:Evidence and Potential Mechanisms

Disturbed cholesterol and glucose homeostasis play crucial roles in the development of various diseases such as cardiovascular diseases,cerebrovascular diseases,central nervous system diseases,and cancer.An increasing number of studies have shown that excessive body fat accumulation is associated with type 2 diabetes or insulin resistance in a vicious cycle.This vicious cycle promotes the occurrence and development of the aforementioned diseases.Therefore,stabilizing the blood lipids and blood glucose of patients is the predominant strategy for improving the symptoms of patients with cardiovascular,cerebrovascular,and central nervous system diseases.Traditional Chinese medicine,mainly Chinese herbal medicine(CHM),has a history of more than 2000 years in China,which has established a unique theory and accumulated a great wealth of clinical experience.Moreover,CHM has been widely used in China and other countries for the treatment of cardiovascular and cerebrovascular diseases,with the advantages of preventing and curing hyperlipidemia,diabetes,hypertension,and other diseases.However,the use of CHM in Western countries remains rather limited,partly because of the incomplete understanding of multiple complex components and uncertain pharmacological mechanisms.Herein,we review and discuss the benefits,molecular mechanisms,and clinical research progress of bioactive components of CHM and their preparations as therapeutics for hyperlipidemia and hyperglycemia.

Development status of novel spectral imaging techniques and application to traditional Chinese medicine

Traditional Chinese medicine(TCM)is a treasure of the Chinese nation,providing effective solutions to current medical requisites.Various spectral techniques are undergoing continuous development and provide new and reliable means for evaluating the efficacy and quality of TCM.Because spectral techniques are noninvasive,convenient,and sensitive,they have been widely applied to in vitro and in vivo TCM evaluation systems.In this paper,previous achievements and current progress in the research on spectral technologies(including fluorescence spectroscopy,photoacoustic imaging,infrared thermal imaging,laser-induced breakdown spectroscopy,hyperspectral imaging,and surface enhanced Raman spectroscopy)are discussed.The advantages and disadvantages of each technology are also presented.Moreover,the future applications of spectral imaging to identify the origins,components,and pesticide residues of TCM in vitro are elucidated.Subsequently,the evaluation of the efficacy of TCM in vivo is presented.Identifying future applications of spectral imaging is anticipated to promote medical research as well as scientific and technological explorations.

Synergistic Mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera Aqueous Extract: Its Liver and Kidney Benefits in Male Albino Rat Model

Background: The synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract is a common drink in Port Harcourt, Nigeria. It is assumed to have various health benefits. However, the synergistic mixture of the content has not been studied scientifically, hence the need to evaluate its effect on the liver and kidney being part of the body’s metabolic organs. Aim: This study evaluated the synergistic mixture of Cyperus esculentus, Phoenix dactylifera and Cocos nucifera (STCD) aqueous extract in male albino rats. Methods: Acute toxicity LD50 of STCD was carried out, afterwards, fifteen male albino rats were grouped into three groups with 5 rats in each group;Control, 200 mg/kg, 400 mg/kg STCD. The rats were administered STCD orally 24 hourly, for 21 days, with feed and water ad libitum. At the end of the experiment, blood samples were collected for biochemical analysis of the liver and kidney biomarkers, while the liver and kidney tissues were harvested for histopathological examination using standard laboratory methods. Descriptive statistics were computed and expressed as Mean ± SD. One-way ANOVA and Turkeys test was performed. P value ≤0.05 was considered statistically significant. Results: Acute toxicity LD50 of STCD was observed to be ≥2404.2 mg/kg body weight. An increase in the percentage body weight difference of 8.39% and 2.86% was observed for 200 and 400 mg/kg STCD groups. Also, the liver weight was observed to increase in 400 mg/kg (3.92 ± 1.42) in comparison to the control group (3.48 ± 1.61), a decrease in the kidney weight was observed in all groups administered STCD in comparison to the control group. Administration of STCD at both 200 and 400 mg/kg revealed a decrease in the concentration of the hepatic biomarkers AST, ALT, ALP, TP, Albumin, Total and conjugated bilirubin. The kidney biomarker Urea was observed to decrease in concentration for 200 mg/kg STCD (4.60 ± 1.83) and 400 mg/kg STCD (4.76 ± 0.74) when compared to the control group (6.32 ± 2.74). A decrease in Creatinine was observed in 200 mg/kg (91.80 ± 34.69) and 400 mg/kg (98.60 ± 15.53) in comparison to the control group (117.60 ± 42.88). The histological examination of the liver of rats administered STCD revealed structural normal central vein, hepatocytes and portal tract. The kidney examination revealed normal glomeruli and normal tubule. Conclusion: The findings of this study opine that STCD improved the health of both the liver and kidney as evidenced via the biomarkers and histological examinations of the liver and kidney. This study therefore recommends the intake of STCD at moderate doses for improved liver and kidney function due to its bioactive compounds and nutritional content.

Association between Support and Satisfaction with Life among Older Adults in Ekiti, Nigeria: Findings and Implications

Many developing countries like Nigeria lack policy for the care of the older adults and this creates major challenges for the elderly population. The traditional family institution and community support that used to be safety nest are being adversely affected by westernization. This development might have adverse effect on life satisfaction among the older adults. This hospital based cross-sectional study was designed to determine the association between support and life satisfaction among older adults. A total of 128 subjects participated in the study out of which 28.9% were satisfied with life. Expectation of support was mainly from the family, less from the community and very low from the government. The level of support received from all sources generally fell short of expectations. Marital status and source of livelihood were significantly associated with life satisfaction. There is inadequate social support from the government and support from family and community fell below expectations. Expectations of support were the most strongly correlated with life satisfaction. Support for older adults must be addressed in order to meet their expectations and improve their level of satisfaction with life.

Thermally degraded palm kernel oil increased serum 4-hydroxynonenal protein adduct formation and hepatotoxic indications in Wistar rats:vitamin C intervention

Objective:The frequent consumption of deep-fried foods has been linked to high risk of certain non-communicable diseases.As a consequence,the safety of deep-fried oil(DFO)ingested with fried foods has been called into question.This study therefore evaluated the effects of DFO from palm kernel on serum 4-hydroxynonenal protein adduct formation,De Ritis ratio(DRR),liver histology and atherogenicity in Wistar rats and the role of vitamin C intervention.Methods:Deep-fried oil samples were characterized for total antioxidant capacity(TAC),degradation and metal contamination levels and compared against counterpart unused frying oil(UFO).In the animal experiment,both oil samples,sourced from commercial cooks,were orally administered,for 13 weeks,to sixty-two rats randomly divided into six test groups of two exposure levels alongside vitamin C control.After exposure,serum liver enzyme activities and lipoproteins levels were determined using colorimetric methods,while protein adducts levels were determined using enzyme-linked immunosorbent assay(ELISA).Histopathological examinations of liver tissues were also performed.Results:DFO had significantly lower(P=0.021)TAC,significantly higher(P=0.024)volatile acid and Pb concentrations compared to UFO.Exposure to DFO significantly increased(P<0.01)serum protein adduct formation,the De Ritis ratio and caused cytoplasmic vacuolation and pigment deposit on liver tissues compared to the control.Additionally,DFO exposures had an initial negative body weight gain rate that increased at the end of the study.Conclusion:However,co-administration of vitamin C significantly reduced(P<0.05)the De Ritis ratio and reduced the serum protein adducts levels by at least 15%.Concomitant intake of vitamin C and DFO can mitigate probable adverse effects.

Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic involvement.Moreover,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable.CASE SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe jaundice.Computed tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated adenocarcinoma.No RAS or BRAF mutations were detected.The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was 2.Biliary drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly initiated.Subsequently,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse events.CONCLUSION Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

Sexual dimorphism of G protein-coupled receptor signaling in the brain

G protein-coupled receptors(GPCRs)represent the most substantial family of membrane receptors that are targeted by U.S.Food and Drug Administration-approved drugs.Much of the preclinical research to understand the pharmacology of many membrane receptors including GPCRs is derived from studies in male animal models(Karp and Reavey,2019).

Neuroinflammation as a therapeutic target in Huntington's disease

In 1872, George Huntington presented his essay “On Chorea” to the Meigs and Mason Academy of Medicine and, in doing so, detailed a disease that would later bear his name. Huntington's disease(HD) is a genetic, neurodegenerative disease that manifests as the loss of motor control,cognitive impairment,and mood and psychiatric changes in paents.

Glial response in the midcingulate cortex in Huntington’s disease

Huntington’s disease(HD)is a genetic disease characterized by the progressive degeneration of the striatum and cortex.Patients can present with a variety of symptoms that can broadly be classified into motor symptoms,inclusive of choreatic movements and rigidity,mood and psychiatric symptoms,such as depression and apathy,and cognitive symptoms,such as cognitive decline.The causal mutation underlying HD results from an expansion of a CAG repeat sequence on the IT15 gene,resulting in the formation and accumulation of a mutant huntingtin protein.

Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative stress.Likewise,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s disease.Therefore,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and neuroinflammation.To better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor UNC0642.We found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)mRNA.Accordingly,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control group.We also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a inhibitor.To confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative insult.In this setting,treatment with G9a inhibitor increases both cell survival and antioxidant enzymes.Moreover,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and apoptosis.In addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers expression.Finally,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a inhibition.Altogether,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

Emergence of taurine as a therapeutic agent for neurological disorders

Taurine is a sulfur-containing,semi-essential amino acid that occurs naturally in the body.It alternates between inflammation and oxidative stress-mediated injury in various disease models.As part of its limiting functions,taurine also modulates endoplasmic reticulum stress,Ca^(2+)homeostasis,and neuronal activity at the molecular level.Taurine effectively protects against a number of neurological disorders,including stro ke,epilepsy,cerebral ischemia,memory dysfunction,and spinal cord injury.Although various therapies are available,effective management of these disorders remains a global challenge.Approximately 30 million people are affected worldwide.The design of taurine fo rmation co uld lead to potential drugs/supplements for the health maintenance and treatment of central nervous system disorders.The general neuroprotective effects of taurine and the various possible underlying mechanisms are discussed in this review.This article is a good resource for understanding the general effects of taurine on various diseases.Given the strong evidence for the neuropharmacological efficacy of taurine in various experimental paradigms,it is concluded that this molecule should be considered and further investigated as a potential candidate for neurotherapeutics,with emphasis on mechanism and clinical studies to determine efficacy.

Gastrointestinal radiation injury:Symptoms,risk factors and mechanisms

Ionising radiation therapy is a common treatment modality for different types of cancer and its use is expected to increase with advances in screening and early detection of cancer.Radiation injury to the gastrointestinal tract is important factor working against better utility of this important therapeutic modality.Cancer survivors can suffer a wide variety of acute and chronic symptoms following radiotherapy,which significantly reduces their quality of life as well as adding an extra burden to the cost of health care.The accurate diagnosis and treatment of intestinal radiation injury often represents a clinical challenge to practicing physicians in both gastroenterology and oncology.Despite the growing recognition of the problem and some advances in understanding the cellular and molecular mechanisms of radiation injury,relatively little is known about the pathophysiology of gastrointestinal radiation injury or any possible susceptibility factors that could aggravate its severity.The aims of this review are to examine the various clinical manifestations of post-radiation gastrointestinal symptoms,to discuss possible patient and treatment factors implicated in normal gastrointestinal tissue radiosensitivity and to outline different mechanisms of intestinal tissue injury.

Gastrointestinal radiation injury:Prevention and treatment

With the recent advances in detection and treatment of cancer,there is an increasing emphasis on the efficacy and safety aspects of cancer therapy.Radiation therapy is a common treatment for a wide variety of cancers,either alone or in combination with other treatments.Ionising radiation injury to the gastrointestinal tract is a frequent side effect of radiation therapy and a considerable proportion of patients suffer acute or chronic gastrointestinal symptoms as a result.These side effects often cause morbidity and may in some cases lower the efficacy of radiotherapy treatment.Radiation injury to the gastrointestinal tract can be minimised by either of two strategies:technical strategies which aim to physically shift radiation dose away from the normal intestinal tissues,and biological strategies which aim to modulate the normal tissue response to ionising radiation or to increase its resistance to it.Although considerable improvement in the safety of radiotherapy treatment has been achieved through the use of modern optimised planning and delivery techniques,biological techniques may offer additional further promise.Different agents have been used to prevent or minimize the severity of gastrointestinal injury induced by ionising radiation exposure,including biological,chemical and pharmacological agents.In this review we aim to discuss various technical strategies to prevent gastrointestinal injury during cancer radiotherapy,examine the different therapeutic options for acute and chronic gastrointestinal radiation injury and outline some examples of research directions and considerations for prevention at a pre-clinical level.

Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions

Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated.

Venous thrombosis and prothrombotic factors in inflammatory bowel disease

Patients with inflammatory bowel disease(IBD)may have an increased risk of venous thrombosis(VTE).PubMed,ISI Web of Knowledge and Scopus were searched to identify studies investigating the risk of VTE and the prevalence of acquired and genetic VTE risk factors and prothrombotic abnormalities in IBD.Overall,IBD patients have a two-to fourfold increased risk of VTE compared with healthy controls,with an overall incidence rate of 1%-8%.The majority of studies did not show significant differences in the risk of VTE between Crohn’s disease and ulcerative colitis.Several acquired factors are responsible for the increased risk of VTEin IBD:inflammatory activity,hospitalisation,surgery,pregnancy,disease phenotype(e.g.,fistulising disease,colonic involvement and extensive involvement)and drug therapy(mainly steroids).There is also convincing evidence from basic science and from clinical and epidemiological studies that IBD is associated with several prothrombotic abnormalities,including initiation of the coagulation system,downregulation of natural anticoagulant mechanisms,impairment of fibrinolysis,increased platelet count and reactivity and dysfunction of the endothelium.Classical genetic alterations are not generally found more often in IBD patients than in nonIBD patients,suggesting that genetics does not explain the greater risk of VTE in these patients.IBD VTE may have clinical specificities,namely an earlier first episode of VTE in life,high recurrence rate,decreased efficacy of some drugs in preventing further episodes and poor prognosis.Clinicians should be aware of these risks,and adequate prophylactic actions should be taken in patients who have disease activity,are hospitalised,are submitted to surgery or are undergoing treatment.

Androgenic regulation of novel genes in the epididymis

The epididymis is critically dependent on the presence of the testis. Although several hormones, such as retinoids and progestins, and factors secreted directly into the epididymal lumen, such as androgen binding protein and fibroblast growth factor, might play regulatory roles in epididymal function, testosterone （T） and its metabolites, dihydrotestosterone （DHT） and estradiol （E2）, are accepted as the primary regulators of epididymal structure and functions, with the former playing the greater role. To ascertain the molecular action of androgens on the epididymis, three complementary approaches were pursued to monitor changes in gene expression in response to different hormonal milieux. The first was to establish changes in gene expression along the epididymis as androgenic support is withdrawn. The second was to determine the sequence of responses that occur in an androgen deprived tissue upon re-administration of the two metabolites of T, DHT and E2. The third was to study the effects of androgen withdrawal and re-administration on gene expression in immortalized murine caput epididymidal principal cells. Specific responses were observed under each of these conditions, with an expected major difference in the panoply of genes expressed upon hormone withdrawal and re-administration; however, some key common features were the common roles of genes in insulin like growth factor/epidermal growth factor and the relatively minor and specific effects of E2 as compared to DHT. Together, these results provide novel insights into the mechanisms of androgen regulation in epididymal principal cells. （Asian J Androl 2007 July; 9： 545-553）