From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Autoantibodies against beta cells to predict early insulin requirements in pediatric patients with clinically diagnosed type 2 diabetes

BACKGROUND Autoimmunity has emerged as a probable disease modifier in patients with clinically diagnosed type 2 diabetes mellitus(T2DM),that is,patients who have insulin resistance,obesity,and other cardiovascular risk factors,suggesting that the presence of glutamic acid decarboxylase(anti-GAD65),islet antigen 2(anti-IA2),and zinc transporter 8(anti-Zn8T)antibodies could have deleterious effects on beta cell function,causing failure and earlier requirement for insulin treatment.AIM To evaluate anti-GAD65,anti-IA2 and anti-Zn8T as predictors of early insulin requirement in adolescents with a clinical diagnosis of T2DM.METHODS This was a case–control study in patients with clinically diagnosed with T2DM(68 cases and 64 controls with and without early insulin dependence respectively),male and female,aged 12–18 years.Somatometry,blood pressure,glucose,insulin,C-peptide,glycated hemoglobin A1c,and lipid profiles were assessed.ELISA was used to measure anti-GAD65,anti-IA2,and anti-Zn8T antibodies.Descriptive statistics,Pearson'sχ2 test,Student's t test,and logistic regression was performed.P<0.05 was considered statistically significant.RESULTS There were 132 patients(53.8%female),with a mean age was 15.9±1.3 years,and there was a disease evolution time of 4.49±0.88 years.The presence of anti-GAD65,anti-IA2,and anti-Zn8T positivity was found in 29.5%,18.2%,and 15.9%,respectively.Dividing the groups by early or no insulin dependence showed that the group with insulin had a higher frequency of antibody positivity:anti-GAD65 odds ratio(OR):2.42(1.112–5.303,P=0.026);anti-IA2:OR:1.55(0.859–2.818,P=0.105);and anti-Zn8T:OR:7.32(2.039–26.279,P=0.002).CONCLUSION Anti-GAD65 positivity was high in our study.Anti-GAD65 and anti-Zn8T positivity showed a significantly depleted beta cell reserve phenotype,leading to an increased risk of early insulin dependence.

Endoscopic ultrasound-guided gastroenterostomy for gastric outlet obstruction in Mexico

BACKGROUND Endoscopic ultrasound-guided gastroenterostomy(EUS-GE)has recently emerged as an alternative treatment for gastric outlet obstruction(GOO)in selected patients.AIM To report the initial experience of EUS-GE in patients with GOO.METHODS This study was a retrospective,observational,multicenter study in which the data from 10 patients who underwent EUS-GE due to GOO between September 2021 and May 2023 were collected.We analyzed technical success,clinical success,adverse events,and survival.Technical success was defined as adequate positioning and deployment of the stent.Clinical success was defined as the patient’s ability to tolerate oral intake without vomiting 7 d after the procedure.Postprocedural adverse events were recorded.RESULTS Eleven procedures in 10 patients with GOO were included.The mean age of the patients was 67.5 years(range:56-77 years).Malignant GOO was present in 9 patients.Technical success was achieved in 9/11 procedures(82%).Among them,clinical success was achieved in 9 patients(100%).Adverse events occurred in 1 patient(9%).The median survival was 3 months(n=7;range:1-8 months).CONCLUSION EUS-GE is a feasible therapeutic option in the treatment of GOO.

Tibolone modulates neuronal plasticity through regulating Tau, GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles （NFTs）; these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone （TIB） have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB （0.01 mg/kg and 1mg/kg, intragastrically for 12 weeks） on the content of total and hyperphosphorylated Tau （PHF-1） proteins and the regulation of GSK3β/Akt/PI3K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB： it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.

Expression of triggering receptor on myeloid cell 1 and histocompatibility complex molecules in sepsis and major abdominal surgery

AIM： To evaluate the surface expression of triggering receptor on myeloid cell 1 （TREM-1）, class Ⅱ major histocompatibility complex molecules （HLA-DR）, and the expression of the splicing variant （svTREH-1） of TREM-1 in septic patients and those subjected to major abdominal surgery. METHODS： Using flow cytometry, we examined the surface expression of TREM-1 and HLA-DR in peripheral blood monocytes from 11 septic patients, 7 elective gastrointestinal surgical patients, and 10 healthy volunteers, svTREM-1 levels were analyzed by RT-PCR. RESULTS： Basal expression of TREM-1 and HLA- DR in healthy volunteers was 35.91±14.75 MFI and 75.8±18.3%, respectively. In septic patients, TREM-1 expression was 59.9±23.9 MFI and HLA-DR expression was 44.39±20.25%, with a significant difference between healthy and septic groups （P〈0.05） for both molecules. In the surgical patients, TREM-1 and HLA-DR expressions were 56.8±20.85 HFI and 71±13.8% before surgery and 72.65±29.92 MFI and 72.82±22.55% after surgery. TREM-1 expression was significantly different （P = 0.0087） between the samples before and after surgery and svTREM-1 expression was 0.8590± 0.1451 MF1, 0.8820±0.1460 MF1, and 2.210±0.7873 MF1 in the healthy, surgical （after surgery） and septic groups, respectively. There was a significant difference （P = 0.048） in svTREM-1 expression between the healthy and surgical groups and the septic group. CONCLUSION： TREM-1 expression is increased during systemic inflammatory conditions such as sepsis and the postoperative phase. Simultaneous low expression of HLA-DR molecules correlates with the severity of illness and increases susceptibility to infection. Additionally, TREM-1 expression is distinctly different in surgical patients at different stages of the inflammatory response before and after surgery. Thus, surface TREM-1 appears to be an endogenous signal during the course of the inflammatory response, svTREM-1 expression is significantly increased during sepsis, appearing to be an indicator of severity of illness. Together, these data indicate that TREM-1 may play an important role in establishing and amplifying the systemic inflammatory response. TREM-1, HLA-DR, and svTREM-1 expression analysis can provide useful diagnostic and prognostic indicators during SIRS, CARS, and sepsis.

Gallstone ileus,clinical presentation,diagnostic and treatment approach

Gallstone ileus is a mechanical intestinal obstruction due to gallstone impaction within the gastrointestinal tract. Less than 1% of cases of intestinal obstruction are derived from this etiology. The symptoms and signs of gallstone ileus are mostly nonspecific. This entity has been observed with a higher frequency among the elderly, the majority of which have concomitant medical illness. Cardiovascular, pulmonary, and metabolic diseases should be considered as they may affect the prognosis. Surgical relief of gastrointestinal obstruction remains the mainstay of operative treatment. The current surgical procedures are:(1) simple enterolithotomy;(2) enterolithotomy, cholecystectomy and fistula closure(one-stage procedure); and(3) enterolithotomy with cholecystectomy performed later(two-stage procedure). Bowel resection is necessary in certain cases after enterolithotomy is performed. Large prospective laparoscopic and endoscopic trials are expected.

Current approach to treatment of minimal hepatic encephalopathy in patients with liver cirrhosis

Minimal hepatic encephalopathy(MHE)corresponds to the earliest stage of hepatic encephalopathy(HE).MHE does not present clinically detectable neurological-psychiatric abnormalities but is characterized by imperceptible neurocognitive alterations detected during routine clinical examination via neuropsychological or psychometrical tests.MHE may affect daily activities and reduce job performance and quality of life.MHE can increase the risk of accidents and may develop into overt encephalopathy,worsening the prognosis of patients with liver cirrhosis.Despite a lack of consensus on the therapeutic indication,interest in finding novel strategies for prevention or reversion has led to numerous clinical trials;their results are the main objective of this review.Many studies address the treatment of MHE,which is mainly based on the strategies and previous management of overt HE.Current alternatives for the management of MHE include measures to maintain nutritional status while avoiding sarcopenia,and manipulation of intestinal microbiota with non-absorbable disaccharides such as lactulose,antibiotics such as rifaximin,and administration of different probiotics.This review analyzes the results of clinical studies that evaluated the effects of different treatments for MHE.

Association between Helicobacter spp.infections and hepatobiliary malignancies:A review

Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma,the bile ducts intrahepatic cholangiocarcinoma and extrahepaticcholangiocarcinoma,the gallbladder and the ampulla of Vater(collectively known as biliary tract cancers).These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies.Cholangiocarcinoma(CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available.Population genetics,geographical and environmental factors,cholelithiasis,obesity,parity,and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors.Other important factors affecting the carcinogenesis of these tumors include chronic inflammation,obstruction of the bile ducts,and impaired bile flow.It has been suggested that CCA is caused by infection with Helicobacter species,such as Helicobacter bilis and Helicobacter hepaticus,in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer.Due to the difficulty in culturing these Helicobacter species,molecular methods,such as polymerase chain reaction and sequencing,or immunologic assays have become the methods of choice for diagnosis.However,clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings,and the use of uniform and validated techniques is needed.

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico.

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

AIM: To investigate the effects of vitamins (A, C and E) on liver injury induced by ethanol administration during liver regeneration in rats. METHODS: Male Wistar rats subjected to 70% partial hepatectomy were divided into five groups (groups 1-5). During the experiment, animals of Group 1 drank only water. The other four groups (2-5) drank 30 mL of ethanol/L of water. Group 3 additionally received vitamin A, those of group 4 vitamin C and those of group 5 received vitamin E. Subsequently serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin and bilirubin were measured colorimetrically. Lipid peroxidation (thiobarbituric-acid reactive substances, TBARS) both in plasma and liver was measured, as well as liver mass gain assessment and total DNA. RESULTS: Compared with sham group, serum AST and ALT increased significantly under ethanol treatment (43% and 93%, respectively, with P < 0.05). Vitamin C and vitamin E treatment attenuated the ethanol-induced increases in ALT and AST activity. Ethanol treatment also decreased serum albumin concentration compared to sham group (3.1 ± 0.4 g/dL vs 4.5 ± 0.2 g/dL; P < 0.05). During liver regeneration vitamins C and E significantly ameliorated liver injury for ethanol administration in hepatic lipid peroxidation (4.92 nmol/mg and 4.25 nmol/mg vs 14.78 nmol/mg, respectively, with P < 0.05). In association with hepatic injury, ethanol administration caused a significant increase in both hepatic and plasma lipid peroxidation. Vitamins (C and E) treatment attenuated hepatic and plasma lipid peroxidation. CONCLUSION: Vitamins C and E protect against liver injury and dysfunction, attenuate lipid peroxidation, and thus appear to be significantly more effective than vitamin A against ethanol-mediated toxic effects during liver regeneration.

Timing, method and discontinuation of hydrocortisone administration for septic shock patients

AIM To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.METHODS This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone.It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31 st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic(ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.RESULTS All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h(range, 47.5-90.5) vs 108 h(range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute(range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute(range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus(83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock(r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81(P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75(P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse(RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio(OR), 5.3; P = 0.04] and hypokalemia(OR = 10.6; P = 0.01). CONCLUSION Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceraltype leishmaniasis are recorded and 60000 persons died from the disease. In Mexico,cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major,while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC_(50)≤30 mg/mL or m M have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

Detection of Mycoplasmas in Patients with Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative disease of the motor neurons and the cause is unknown. Diverse factors such as genetic defects, nutritional deficiencies, head trauma, environmental toxin, autoimmune responses and viral and bacterial infections are involved. Mycoplasmas have been implicated as causal agents of different illnesses in human. The purpose of this study was to investigate the presence of mycoplasmas in the bloodstream of patients with ALS. Patients with ALS and healthy individuals were included in the study. A blood sample was taken in tubes with or without anticoagulant. Mycoplasmas were detected by culture or direct PCR, and the presence of antibodies IgM and IgG against LAMPs of these microorganisms by Western blot. Cultures for aerobic facultative bacteria were also done. Blood samples from 13 patients and 44 healthy individuals were screened. All blood cultures for non-fermentative mycoplasmas and aerobic facultative bacteria were negative. Cultures for fermentative mycoplasmas were considered positive after identification of mycoplasmal DNA by PCR. Mycoplasma sp. was detected by culture or direct PCR in 6/13 (46%) patients and in 4/44 (9%) of healthy individuals. M. fermentans was detected by PCR using specific primers in six patients and in two healthy individuals. IgM against LAMPs of M. fermentans were detected in 6/13 (46%) blood samples from patients and in 13/44 (30%) from healthy individuals, while. IgG was detected in 4/13 (31%) patients and in 3/44 (7%) healthy individuals. The results of this study show that mycoplasmas cause a systemic infection and could play a role in the origin or progression of the ALS.

Novel LIPA mutations in Mexican siblings with lysosomal acid lipase deficiency

Lysosomal acid lipase(LAL) deficiency is an underrecognized lysosomal disease caused by deficient enzymatic activity of LAL.In this report we describe two affected female Mexican siblings with early hepatic complications.At two months of age,the first sibling presented with alternating episodes of diarrhea and constipation,and later with hepatomegaly,elevated transaminases,high levels of total and low-density lipoprotein cholesterol,and low levels of highdensity lipoprotein.Portal hypertension and grade 2 esophageal varices were detected at four years of age.The second sibling presented with hepatomegaly,elevated transaminases and mildly elevated lowdensity lipoprotein and low high-density lipoprotein at six months of age.LAL activity was deficient in both patients.Sequencing of LIPA revealed two previously unreported heterozygous mutations in exon 4:c.253C>A and c.294C>G.These cases highlight the clinical continuum between the so-called Wolman disease and cholesteryl ester storage disease,and underscore that LAL deficiency represents a single disease with a degree of clinical heterogeneity.

Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

Oxidative stress （OS） is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone （TIB）, a synthetic hormone used as a treatment for menopausal ymptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone （O3） exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β （GSK3β）, and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups： control group （ozone-free air plus vehicle [C]）, control ＋ TIB group （ozone-free air plus TIB 1 mg/kg [C ＋ TIB]）; 7,15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 ＋ TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods （Marklund and TBARS, respectively）. We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment （over 15 days） with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results suggest a beneficial use of hormone replacement therapy with TIB to prevent neurodegeneration caused by O3 exposure in rats.

Neuroprotective effect of immunomodulatory peptides in rats with traumatic spinal cord injury

Several therapies have shown obvious effects on structural conservation contributing to motor functional recovery after spinal cord injury(SCI).Nevertheless, neither strategy has achieved a convincing effect.We purposed a combined therapy of immunomodulatory peptides that individually have shown significant effects on motor functional recovery in rats with SCI.The objective of this study was to investigate the effects of the combined therapy of monocyte locomotion inhibitor factor(MLIF), A91 peptide, and glutathione monoethyl ester(GSH-MEE) on chronic-stage spinal cord injury.Female Sprague-Dawley rats underwent a laminectomy of the T9 vertebra and a moderate contusion.Six groups were included: sham, PBS, MLIF + A91, MLIF + GSH-MEE, A91 + GSH-MEE, and MLIF + A91 + GSH-MEE.Two months after injury, motor functional recovery was evaluated using the open field test.Parenchyma and white matter preservation was evaluated using hematoxylin & eosin staining and Luxol Fast Blue staining, respectively.The number of motoneurons in the ventral horn and the number of axonal fibers were determined using hematoxylin & eosin staining and immunohistochemistry, respectively.Collagen deposition was evaluated using Masson's trichrome staining.The combined therapy of MLIF, A91, and GSH-MEE greatly contributed to motor functional recovery and preservation of the medullary parenchyma, white matter, motoneurons, and axonal fibres, and reduced the deposition of collagen in the lesioned area.The combined therapy of MLIF, A91, and GSH-MEE preserved spinal cord tissue integrity and promoted motor functional recovery of rats after SCI.This study was approved by the National Commission for Scientific Research on Bioethics and Biosafety of the Instituto Mexicano del Seguro Social under registration number R-2015-785-116(approval date November 30, 2015) and R-2017-3603-33(approval date June 5, 2017).

Anti-inflammatory evaluation and acute toxicity of three food supplements that contain Moussonia deppeana

Objective:To identify the anti-inflammatory activity through two murine models and in the median Lethal Dose(LD_(50)) of three dietary supplements that contain Moussonia deppeana.Methods:The anti-inflammatory activity of three dietary supplements(Cicatrisan/Gastricus^(R),Gastinol^(R),and Gastrovita^(R)) EtOH extracts was evaluated by TPA and by carrageenan murine models;also,median Lethal Dose(LD_(50)) was determined.Verbascoside was quantified by High-Performance Liquid Chromatography.β-sitosterol,stigmasterol and the mixture of ursolic and oleanolic acids were identified in all supplements by TLC;however,none of these dietary supplements contain verbascoside.Results:For the TPA model,Cicatrisan/Gastricus^(R)generated a notable effect with 38.24%inhibition.While in the carrageenan model,it also exhibited noteworthy anti-inflammatory activity of ear edema with 66.39%of paw edema inhibition at 150 mg/kg,followed by Gastinol^(R) and Gastrovita^(R) with 50%at 300 mg/kg.Finally,LD_(50) was >2 g/kg for all supplements,when was administered intragastrically and Body Weight(BW) gain in mice was not altered after 14 days.Conclusions:Of the three food supplements containing M.deppeana,only the EtOH extract from the Cicatrisan/Gastricus^(R)formulation(tablets) showed significant anti-inflammatory activity in both experimental models and the LD_(50) was > 2 g/kg.

Insulinoma after sleeve gastrectomy:A case report

BACKGROUND Laparoscopic sleeve gastrectomy(LSG)has been proposed as an effective and durable treatment for severe obesity and glucose metabolism disorders,and its prevalence has increased from 5%to 37%since 2008.One common complication after bariatric surgery is a postprandial hyperinsulinemic hypoglycemic state.While rare,insulinomas can cause this state,where symptoms are more common in the fasting state;thus,evaluation of insulin secretion is needed.Until now,there have been no reports of insulinoma after LSG.CASE SUMMARY We describe the case of a 43-year-old woman who was referred to the obesity clinic 2 years after LSG was performed.She had symptoms of hypoglycemia predominantly in the fasting state and documented hypoglycemia of less than 30 mg/d L,which are compatible with Whipple’s triad.Initially,dumping syndrome was suspected,but after a second low fasting plasma glucose was documented,a 72-h fasting test was performed that tested positive.Computed tomography and endoscopic ultrasound were performed,identifying the presence of a homogeneous hypoechoic semioval tumoral lesion in the pancreas.The diagnosis was compatible with insulinoma.After laparoscopic enucleation of the insulinoma,the symptoms and hypoglycemia disappeared.The histopathological report described a well-differentiated grade 2 neuroendocrine tumor with positive chromogranin and synaptophysin and Ki67 immunopositivity in 4%of the neoplastic cells.CONCLUSION Insulinoma after LSG is a rare condition,and clinicians must be aware of it,especially if the patient has hypoglycemic symptoms during the fasting state.

Tick-Borne Rickettsial Pathogens in Rodents from Mexico

Tick-Borne Rickettsial Diseases (TBRD) are emerging zoonotic diseases, and a problem of human health and veterinary medication. The distribution of these diseases is related to the distribution of vector. The presence of pathogens in the host is a risk indicator of population exposure to these areas. A total of 478 tissues samples from rodents, A. phagocytophilum 18 (3.7%), E. canis 47 (9.8%), Rickettsia rickettsii 18 (3.7%) and E. chaffeensis 19 (3.9%) were detected using species-specific PCR assay. It is the first report in Mexico the presence of rodents infected with A. phagocytophilum and E. chaffeensis. The rodent Peromyscus spp. were the most commonly prevalent host of infection for all the bacteria’s. We have to consider as host of TBRD transmitter and provide a useful contribution to understanding their epidemiology. The health sector should be considered all the fevers of unknown causes in humans and animals in Mexico as infections by these vector-borne rickettsial pathogens.

Pulmonary arterial hypertension associated with systemic sclerosis: Current diagnostic approach and therapeutic strategies

Pulmonary arterial hypertension(PAH) represents a devastating vascular complication of systemic sclerosis(SSc) and is found in 10%-15% of cases carrying a severe prognosis. PAH has a dramatic impact on the clinical course and overall survival, being the single most common cause of death in patients with this entity. The clinical course and aggressive progression of PAH has led clinicians to perform annual screening for it, since early detection and diagnosis are the cornerstone of a prompt therapeutic intervention. The diagnosis of PAH can be challenging to clinicians, particularly in its early stages, since in the context of SSc, the multiple causes of dyspnea need to be assessed. Doppler echocardiography represents the best initial screening tool, however, right heart catheterization remains the gold standard and definitive diagnostic means. Remarkable advances have been achieved in elucidating the pathogenesis of PAH in the past two decades, leading to the development of disease-specific targeted therapies: prostacyclin analogues, endothelin receptor antagonists and inhibitors of five phosphodiesterase pathways. However, the clinical response to these therapies in SSc-associated PAH has not been as great as the one seen with idiopathic PAH. This review also focuses on the diagnosis and novel therapies that are currently available for PAH, as well as potential future therapeutic developments based on newly acquired knowledge of diverse pathogenic mechanisms.