Incomplete functional and morphological recovery after acute and acute recurrent pancreatitis in children.

BACKGROUND AND AIM: There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. METHODS: All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (µg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DIo ) (mmol/L) (ß-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. RESULTS: At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ± 150.94 (AP), 135.70 ± 103.80 (ARP), 46.56 ± 30.20 (CP), and 240.00 ± 181.83 (HC) (P < 0.001; anova) (AP vs CP, ARP vs CP, and CP vs HC; P < 0.001). Prediabetes due to insulin resistance was seen in 16.6% and 22.6% (P = 0.56) of AP and ARP. Median (interquartile range) DIo (mmol/L) was comparable between AP (4.20 [2.36, 8.3]) and HC (5.20 [2.89, 8.68]), but was low in ARP (2.97 [1.80, 5.12]), which was comparable with CP (1.91 [1.20, 2.83]). Endoscopic ultrasound demonstrated morphological changes in 25% and 37% (P = 0.34) of AP and ARP, respectively. CONCLUSION: There was high frequency of biochemical evidence of exocrine insufficiency. ß-Cell function (DIo ) was preserved among AP but was poor in ARP. Nearly one-third showed morphological changes in imaging.

Assessment of genotoxicity amongst smokers, alcoholics, and tobacco chewers of North India using micronucleus assay and urinary 8-hydroxyl-2'-deoxyguanosine, as biomarkers.

The main objective of the present study was to screen the genotoxicity caused by individual and combined habits of smoking, tobacco chewing, and alcohol consumption in human population of North India. Study recruited 67 male subjects aged 25 to 65 years. Buccal mucosal cells were subjected to micronucleus (MN) assay, and 8-hydroxyl-2-deoxyguanosine (8-OHdG) was estimated in their urine samples. Number and shape of the MN cells varied in the buccal epithelium of different groups. Maximum number of MN (0.47%) were found in tobacco chewers followed by smokers (0.45%) and alcoholics (0.44%) (P < 0.05). These results reciprocated the concentration of urinary 8-OHdG. Maximum value for 8-OHdG was also recorded in tobacco chewers (21.07 ± 5.51 mg/mg creatinine) followed by smokers (20.25 ± 3.96 mg/mg creatinine) and alcoholics (19.06 ± 3.41 mg/mg creatinine) (P < 0.05). Combined effects of these agents were found to be statistically different from individual effects. Carcinogenic compounds present in cigarette smoke, nitrosamines found in solid tobacco, and acetaldehyde, a metabolic product of alcohol, induce oxidative stress that manifests into genotoxicity. In conclusion, demographical differences occur in the genotoxicity caused by these three habits. MN assay and urinary 8-OHdG are simple, noninvasive, and reliable biomarkers of genotoxicity.

Malabsorption, Orocecal Transit Time and Small Intestinal Bacterial Overgrowth in Type 2 Diabetic Patients: A Connection.

Type 2 diabetes mellitus consists of dysfunctions characterized by hyperglycemia and resulting from combination of resistance to insulin action and inadequate insulin secretion. Most of diabetic patients report significant gastrointestinal symptoms. Entire GI tract can be affected by diabetes from oral cavity to large bowel and anorectal region. Proteins, carbohydrates, fats, and most fluids are absorbed in small intestine. Malabsorption may occurs when proper absorption of nutrients does not take place due to bacterial overgrowth or altered gut motility. The present study was planned to measure various malabsorption parameters in type 2 diabetic patients. 175 patients and 175 age and sex matched healthy controls attending Endocrinology Clinic in PGI, Chandigarh were enrolled. Lactose intolerance was measured by using non-invasive lactose hydrogen breath test. Urinary d-xylose and fecal fat were estimated using standard methods. Orocecal transit time and small intestinal bacterial overgrowth were measured using non-invasive lactulose and glucose breath test respectively. Out of 175 diabetic patients enrolled, 87 were males while among 175 healthy subjects 88 were males. SIBO was observed in 14.8 % type 2 diabetic patients and in 2.8 % of controls. There was statistically significant increase (p < 0.002) in OCTT in type 2 diabetic patients compared with controls. OCTT was observed to be more delayed (p < 0.003) in patients who were found to have SIBO than in patients without SIBO. Lactose intolerance was observed in 60 % diabetic patients and 39.4 % in controls. Urinary d-xylose levels were also lower in case of diabetic patients but no significant difference was found in 72 h fecal fat excretion among diabetic patients and controls. Urinary d-xylose and lactose intolerance in SIBO positive type 2 diabetic patients was more severe as compared to SIBO negative diabetic patients. From this study we can conclude that delayed OCTT may have led to SIBO which may have instigated the process of malabsorption among type 2 diabetic patients.

Current evidence and future perspectives on the effective practice of patient-centered laboratory medicine.

BACKGROUND: Systematic evidence of the contribution made by laboratory medicine to patient outcomes and the overall process of healthcare is difficult to find. An understanding of the value of laboratory medicine, how it can be determined, and the various factors that influence it is vital to ensuring that the service is provided and used optimally. CONTENT: This review summarizes existing evidence supporting the impact of laboratory medicine in healthcare and indicates the gaps in our understanding. It also identifies deficiencies in current utilization, suggests potential solutions, and offers a vision of a future in which laboratory medicine is used optimally to support patient care. SUMMARY: To maximize the value of laboratory medicine, work is required in 5 areas: (a) improved utilization of existing and new tests; (b) definition of new roles for laboratory professionals that are focused on optimizing patient outcomes by adding value at all points of the diagnostic brain-to-brain cycle; (c) development of standardized protocols for prospective patient-centered studies of biomarker clinical effectiveness or extraanalytical process effectiveness; (d) benchmarking of existing and new tests in specified situations with commonly accepted measures of effectiveness; (e) agreed definition and validation of effectiveness measures and use of checklists for articles submitted for publication. Progress in these areas is essential if we are to demonstrate and enhance the value of laboratory medicine and prevent valuable information being lost in meaningless data. This requires effective collaboration with clinicians, and a determination to accept patient outcome and patient experience as the primary measure of laboratory effectiveness.

Role of oxidative stress & antioxidant defence in ulcerative colitis patients from north India.

BACKGROUND & OBJECTIVES: Oxidative stress contributes to severity of ulcerative colitis (UC) but the status of erythrocyte antioxidant defence remains unknown. The present study was aimed to study the role of oxidative stress and antioxidant levels in erythrocytes of UC patients from north India. METHODS: A total of 81 adult UC patients and 85 age and sex matched apparently healthy controls were included in this study. Levels of lipid peroxidation (LPO), reduced glutathione (GSH), catalase and superoxide dismutase (SOD) were measured in erythrocytes. RESULTS: Mean age of UC patients was 43.5 yr (range 18-64 yr) while in the control group this was 45.3 yr (range 20-64 yr). LPO, catalase and SOD levels in UC patients were significantly increased (P< 0.05) compared to healthy controls, while GSH levels in UC patients were significantly decreased (P< 0.05) compared to healthy controls Ulcerative colitis activity score (UCAI) was 157.4±27.6 in UC patients. INTERPRETATION & CONCLUSIONS: Increased levels of LPO, SOD, catalase and a decreased level of GSH represent that oxidative stress plays a significant role in pathophysiology of UC. Further, the levels of LPO, GSH, catalase and SOD remained same during different UCAI.

N-acetyltransferase 2, cytochrome P4502E1 and glutathione S-transferase genotypes in antitubercular treatment-induced hepatotoxicity in North Indians.

WHAT IS KNOWN AND OBJECTIVE: Tuberculosis (TB) is a major cause of illness and death in developing countries. Hepatotoxicity is a serious side effect of antituberculosis treatment (ATT). NAT2, CYP2E1 and glutathione S-transferase (GST) gene polymorphisms may play an important role in ATT-induced hepatotoxicity. So, elucidating the genetics involved in anti-TB drug-induced hepatotoxicity in patients would be of utmost clinical significance. Therefore, the objective of the study was to elucidate the role of NAT2, CYP2E1 and GST gene polymorphisms in ATT-induced hepatotoxicity in North Indian patients. METHODS: Three hundred patients with pulmonary and extra-pulmonary TB were enrolled. Total genomic DNA was isolated from each patient's peripheral lymphocytes using phenol-chloroform method, and genetic polymorphic analysis for N-acetyltransferase 2 (NAT2), cytochrome P4502E1 (CYP2E1) and GST was performed by polymerase chain reaction (PCR) with restriction fragment length polymorphism (RFLP). RESULTS AND DISCUSSION: Of the 300 patients, 185 were males and 115 females. Among them, 33 males and 22 females developed ATT-induced hepatotoxicity. There were significant increases in alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with ATT-induced hepatotoxicity at 1 month of treatment. NAT2 5/7 and 6/7 were significantly higher in hepatotoxicity patients as compared to the non-hepatotoxicity group. c1/c1 allele of CYP2E1 gene was lower (50·9%) in ATT-induced hepatotoxicity patients as compared to non-hepatotoxicity patients (61·2%), whereas c1/c2 and c2/c2 alleles were higher, but not statistically significant. GSTM1 was significantly higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, whereas GSTT1 and GSTT1/M1 were lower, but not statistically significant. WHAT IS NEW AND CONCLUSION: This study indicates that patients with slow-acetylator genotypes (NAT2 5/7, 6/7) and GSTM1 allele of GST enzyme were at higher risk of ATT-induced hepatotoxicity.

Small intestinal bacterial overgrowth and orocecal transit time in patients of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) consists of Ulcerative colitis (UC) and Crohn's disease (CD). These two conditions share many common features-diarrhea, bloody stools, weight loss, abdominal pain, fever and fatigue. Small intestinal bacterial overgrowth (SIBO) is frequent in patients with CD but it has not been studied in UC Indian patients. AIM: The study was planned to measure orocecal transit time (OCTT) and SIBO in UC and CD patients. METHODS: One hundred thirty-seven patients of IBD (95 UC and 42 CD) and 115 healthy controls were enrolled. OCTT and SIBO were measured by lactulose and glucose hydrogen breath test respectively. Concentration of hydrogen and methane were measured by SC microlyser from Quintron, USA. RESULTS: Mean±standard deviation (SD) of OCTT in patients of IBD was significantly higher as compared to controls. Furthermore, OCTT was significantly higher in CD patients as compared to UC patients. It was also observed that occurrence of SIBO was significantly higher in IBD patients as compared to controls. The occurrence of SIBO in CD (45.2%) was significantly higher as compared to patients in UC (17.8%) group. Percentage of methane positive IBD patients (2.9%) was significantly lower as compared to methane positive controls (24.4%). CONCLUSION: OCTT was significantly delayed in IBD patients as compared to controls and in CD patients as compared to UC patients. OCTT was significantly higher in SIBO positive IBD patients as compared to SIBO negative patients. Thus, we can suggest that delayed OCTT would have been the cause of increased SIBO in these patients.

Combined Effects of Fluoride and Arsenic on Mitochondrial Function in the Liver of Rat.

Biochemical and/or molecular mechanisms of arsenic or fluoride toxicity in experimental animals have been widely investigated in the recent past. However, their combined effects on target cells/organelle are poorly understood. The present study was executed to delineate their combined effects on mitochondrial function in the liver of rat. Female Wistar rats (140 ± 20 g) were force fed individually or in combination with sodium arsenate (4 mg/kg body weight) and sodium fluoride (4 mg/kg body weight) for 90 days. Thereafter, established markers of mitochondrial function viz. mitochondrial lipid peroxidation, oxidative phosphorylation, ATPase, succinic dehydrogenase, and caspase-3 activity were determined. Cytochrome C release and oxidative DNA damage were also estimated in the liver of respective groups of rats. The study showed significant differences in these results amongst the three groups. Observations on parameters viz. LPO, cytochrome-C, caspase-3, and 8-OHdG suggested an antagonistic relationship between these two elements. Results on ATPase, SDH, and ADP:O ratio indicated synergism. It is concluded that AsIII + F in combination may express differential effects on signalling pathways and proapoptotic/antiapoptotic proteins/genes that contribute to liver cell death. Interaction of As and F with mitochondria.

NMR spectroscopy-based analysis of gallstones of cancerous and benign gallbladders from different geographical regions of the Indian subcontinent.

Analysis of the chemical composition of gallstones is vital for the etiopathogenesis of gallstone diseases that can ultimately help in the prevention of its formation. In the present study, gallstones from seven different regions of India were analyzed to highlight the major difference in their composition. Also, gallstones of different pathological conditions i.e., benign (chronic cholecystitis, CC) and malignant gallbladder disease (gallbladder cancer GBC) were characterized. The type of polymorphs of cholesterol molecules was also studied to provide insight into the structure of gallstones. 1H solution state NMR spectroscopy 1D experiments were performed on a total of 94 gallstone (GS) samples collected from seven different geographical regions of India. Solid-State NMR spectroscopy 13C cross-polarization magic angle spinning (CPMAS) experiments were done on the 20 CC GS samples and 20 GBC GS samples of two regions. 1H NMR spectra from the solution state NMR of all the stones reveal that cholesterol was a major component of the maximum stones of the north India region while in south Indian regions, GS had very less cholesterol. 13C CPMAS experiments reveal that the quantity of cholesterol was significantly more in the GS of CC in the Lucknow region compared with GBC stones of Lucknow and Chandigarh. Our study also revealed that GS of the Lucknow region of both malignant and benign gallbladder diseases belong to the monohydrate crystalline form of cholesterol while GS of Chandigarh region of both malignant and benign gallbladder diseases exists in both monohydrate crystalline form with the amorphous type and anhydrous form. Gallstones have a complicated and poorly understood etiology. Therefore, it is important to understand the composition of gallstones, which can be found in various forms and clinical conditions. Variations in dietary practices, environmental conditions, and genetic factors may influence and contribute to the formation of GS. Prevention of gallstone formation may help in decreasing the cases of gallbladder cancer.

Comparison of lactulose and glucose breath test for diagnosis of small intestinal bacterial overgrowth in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Validity of the lactulose breath test (LBT) to diagnose small intestinal bacterial overgrowth (SIBO) has been questioned. Therefore, a study was planned to compare LBT with glucose breath test (GBT) to diagnose SIBO in irritable bowel syndrome (IBS) patients and controls. METHODS: 175 diarrhea-predominant IBS patients and 150 apparently healthy controls were enrolled. IBS was diagnosed according to Rome II criteria. Breath samples were collected every 10 min up to 180 min. Breath H2 and CH4 were measured using an SC MicroLyzer. SIBO was positive with a sustained increase in breath H2 or CH4 or both ≥10 ppm over a baseline value within <90 min in case of LBT and within <120 min in GBT. RESULTS: SIBO was positive in 60/175 (34.3%) patients by lactulose and in 11/175 (6.2%) patients by GBT. In controls, LBT was positive for SIBO in 45/150 (30%) patients and in 1/150 (0.66%) patients by GBT. Positive LBT for SIBO was not significantly different in patients and controls; while using GBT, SIBO was significantly higher (p < 0.01) in patients as compared to controls. By using GBT as gold standard for SIBO, sensitivity, specificity, positive predictive value and negative predictive value of LBT in IBS patients was 63.6, 67.7, 11.7 and 96.6% respectively. CONCLUSION: LBT is not a good test to discriminate SIBO in IBS patients from controls.

Intake of antioxidants and their status in chronic kidney disease patients.

OBJECTIVE: To evaluate the intake and status of antioxidants in chronic kidney disease (CKD) patients. DESIGN: Randomized control trial. SETTING: Hospital outpatient department. SUBJECTS: One hundred eighty-five subjects (145 predialysis CKD patients and 40 apparently healthy controls) were enrolled for this study. The patients were divided into moderate and severe renal failure groups based on their creatinine and glomerular filtration rates. INTERVENTION: All patients completed a food frequency questionnaire, 24-hour dietary recall form, and anthropometric measurements and underwent biochemical and antioxidant lab tests. MAIN OUTCOME MEASURES: Dietary intake, anthropometry, biochemical measures of blood and antioxidant enzymes as well as oxidative stress. RESULTS: Overall, the diet was significantly lower in antioxidant-rich food intake in all the CKD patients as compared with controls. The oxidative stress measured in blood was found to be in consonance with the intake from diet. CONCLUSION: Micronutrients play a major role in the antioxidant status of the patients and must be monitored, as deficiency of these might elevate the oxidative stress of the body, especially in the chronic diseases.

Pro-inflammatory and anti-inflammatory cytokine response in diarrhoea-predominant irritable bowel syndrome patients.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is referred to as a functional bowel disorder which is diagnosed by a number of characteristic symptoms (Rome II criteria) in the absence of detectable structural abnormalities. Low-grade inflammation of the intestine may be one of the reasons for development of diarrhoea-predominant IBS (IBS-D). We undertook this study to estimate the serum levels of pro-inflammatory (IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines in IBS-D patients. METHODS: A total of 108 diarrhoea patients were screened. Out of these only 63 adult IBS-D patients were enrolled. Age and sex matched 62 apparently healthy controls with no GI symptoms were also recruited. Out of 63 IBS-D patients, 37 were males while there were 32 males among the controls. The patients with IBS-D were diagnosed according to the Rome II criteria. Levels of serum IL-6, TNF-alpha and IL-10 were measured in all subjects using ELISA. RESULTS: Mean (+/- SD) age of IBS-D patients (42.6 +/- 19.5 years) was comparable (p = 0.64) to that of controls (43.5 +/- 18.7 years). The mean (+/- SD) levels of IL-6 in IBS-D patients (32.2 +/- 12.01 pg/ml) was significantly higher (p < 0.001) than in controls (7.48 +/- 2.55 pg/ml). The levels of TNF-alpha in IBS-D patients (16.3 +/- 5.2 pg/ml) were also significantly higher (p < 0.05) than in controls (7.94 +/- 2.19 pg/ml). There was no significant difference in the serum levels of IL-10 (p = 0.23) between IBS-D patients (5.75 +/- 2.1 pg/ml) and controls (5.84 +/- 1.9 pg/ml). CONCLUSION: Our results indicate that mild inflammation is involved in IBS-D patients as proinflammatory cytokines were increased although no difference in anti-inflammatory cytokine was observed.

Significance of Inflammation and Apoptosis in Hepatocellular Death in Rat, Co-treated with Arsenic and Fluoride.

Health effects elicited by combined environmental exposures to xenobiotics, in many instances, still remain unresolved. One of these examples is the combined toxicity of arsenic and fluoride. The present study was undertaken to delineate the role of inflammation and apoptosis in hepatocellular death caused by co-exposure to arsenic and fluoride in rat. Sodium arsenate (4 mg/kg body weight) and sodium fluoride (4 mg/kg body weight) were administered to female Wistar rats, individually and in combination, for 90 days. Results on tumor necrotic factor-α (TNF-α), interleukin-12 (IL-12), and comet assay showed increased values in comparison to those obtained in arsenic- or fluoride-treated rats. Results on NO, TBARS, and caspase-9 showed higher values than fluoride-treated rats but lower levels than arsenic-treated rats. It is hypothesized that increased generation of nitric oxide induces the release of cytokines that activates caspase-9. Caspase-9 promotes the synthesis of caspase-3 that executes apoptosis. Histopathological observations on apoptotic bodies and Kupffer cells support these observations.

Zinc Oxide Nanoparticles Ameliorate Dimethylnitrosamine-Induced Renal Toxicity in Rat.

Dimethylnitrosamine (DMN) is an established carcinogen. It is toxic to several organs, viz., the liver, kidney, and lungs, and immune system. Several drugs have been used in the past to modulate its toxicity using experimental animal models. The present study was designed to investigate the effect of zinc oxide nanoparticles (ZnONPs) on renal toxicity caused by DMN in laboratory rat. Since oxidative mechanisms are mainly involved in its toxicity, the proposed study focuses on the amelioration of oxidative stress response by ZnONPs, if any. The present results show that administration of ZnONPs (50 mg/kg body weight/rat) to DMN (2 µl/100 g body weight/rat)-treated rats diminuted the concentration of malonaldehyde, H2O2, and NO in the kidney. However, reduced glutathione (GSH) concentration increased after ZnONP treatment. Results on glutathione S-transferase and glutathione peroxidase favored its antioxidative effects. These results are supported by the recovery of oxidative DNA damage and less pronounced histopathological changes in the kidney. It is hypothesized that ZnONPs might be toxic to renal tissue; however, its strong therapeutic/antioxidative potential helps in ameliorating DMN-induced renal toxicity in rat.

Emerging role of artificial intelligence in therapeutics for COVID-19: a systematic review.

To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and pre-print original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug discovery. Only four studies used AI technology for vaccine development, whereas one study generated stable antibodies against SARS-CoV-2. Approx. 50% of studies exclusively targeted 3CLpro of SARS-CoV-2, and only two studies targeted ACE/TMPSS2 for inhibiting host viral interactions. Around 16% of the identified drugs are in different phases of clinical evaluation against COVID-19. AI has emerged as a promising solution of COVID-19 therapeutics. During this current pandemic, many of the researchers have used AI-based strategies to process large databases in a more customized manner leading to the faster identification of several potential targets, novel/repurposing of drugs and vaccine candidates. A number of these drugs are either approved or are in a late-stage clinical trial and are potentially effective against SARS-CoV2 indicating validity of the methodology. However, as the use of AI-based screening program is currently in budding stage, sole reliance on such algorithms is not advisable at this current point of time and an evidence based approach is warranted to confirm their usefulness against this life-threatening disease. Communicated by Ramaswamy H. Sarma.

Asian-Pacific consensus on small intestinal bacterial overgrowth in gastrointestinal disorders: An initiative of the Indian Neurogastroenterology and Motility Association.

In the clinical setting, small intestinal bacterial overgrowth (SIBO) is a frequent, but under-diagnosed entity. SIBO is linked to various gastrointestinal (GI) and non-GI disorders with potentially significant morbidity. The optimal management of SIBO is undefined while there is a lack of published consensus guidelines. Against this background, under the auspices of the Indian Neurogastroenterology and Motility Association (INMA), formerly known as the Indian Motility and Functional Diseases Association (IMFDA), experts from the Asian-Pacific region with extensive research and clinical experience in the field of gut dysbiosis including SIBO developed this evidence-based practice guideline for the management of SIBO utilizing a modified Delphi process based upon 37 consensus statements, involving an electronic voting process as well as face-to-face meetings and review of relevant supporting literature. These statements include 6 statements on definition and epidemiology; 11 on etiopathogenesis and pathophysiology; 5 on clinical manifestations, differential diagnosis, and predictors; and 15 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservations was 80% or higher, the statement was regarded as accepted. The members of the consensus team consider that this guideline would be valuable to inform clinical practice, teaching, and research on SIBO in the Asian-Pacific region as well as in other countries.

Garlic in health and disease.

The present article reviews the historical and popular uses of garlic, its antioxidant, haematological, antimicrobial, hepatoprotective and antineoplastic properties and its potential toxicity (from sulfoxide). Garlic has been suggested to affect several cardiovascular risk factors. It has also been shown that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. Since garlic and its constituents can suppress carcinogen formation, bioactivation and tumour proliferation, it is imperative that biomarkers be established to identify which individuals might benefit most. Garlic powder, aged garlic and garlic oil have demonstrated antiplatelet and anticoagulant effects by interfering with cyclo-oxygenase-mediated thromboxane synthesis. Garlic has also been found to have synergistic effects against Helicobacter pylori with a proton pump inhibitor. The active compound allicin may affect atherosclerosis not only by acting as an antioxidant, but also by other mechanisms, such as lipoprotein modification and inhibition of LDL uptake and degradation by macrophages. Freshly prepared garlic homogenate protects against isoniazid+rifampicin-induced liver injury in experimental animal models. Several mechanisms are likely to account for this protection.

Possible Mechanisms of Liver Injury Induced by Cadmium Sulfide Nanoparticles in Rat.

Cadmium is primarily utilized in the construction of particles known as quantum dots. Hepatotoxicity caused by microparticles of cadmium is very well known; however, toxicity of nanoparticles of cadmium is not well understood. The present study describes the toxicity of cadmium sulfide nanoparticles (CdSNPs) in the liver of rat. Adult Wistar rats were administered CdSNPs (10 mg/kg) on alternate days for 45 days. Serum enzymes (ALT, AST, ALP), biomarkers of lipid peroxidation (MDA, H2O2, and NO), and metallothionein concentration were determined. Histopathological and TEM observations were also made to record morphological changes. CdSNPs (10 mg/kg) induced significant changes in the structure and function of liver. Values of serum enzymes and reactive species increased significantly in rats treated with CdSNPs in comparison to CdS-treated rats. Histopathological observations showed extensive parenchymal degeneration. Ultrastructural studies exhibited proliferation of endoplasmic reticulum, microsomes, and lysosomes. It is concluded that NP-membrane interaction leads to the generation of reactive species that alter membrane integrity and induce oxidative stress. These events may activate cell death pathways in hepatocytes.

Hepatoprotection by carotenoids in isoniazid-rifampicin induced hepatic injury in rats.

This study evaluates the hepatoprotective effect of carotenoids against isoniazid (INH) and rifampicin (RIF). Thirty-six adult rats were divided into the following 4 groups: (1) control group treated with normal saline; (2) INH + RIF group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each; (3) INH + RIF+ carotenoids group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each and 10 mg·(kg body mass)-1·day-1 of carotenoids; and (4) carotenoids group treated with 10 mg·(kg body mass)-1·day-1 of carotenoids for 28 days intragastrically. Oxidative stress and antioxidant levels in liver and blood, liver histology and change in transaminases were measured in all the above-mentioned groups. There was an increase in lipid peroxidation with a reduction in thiols, catalase, and superoxide dismutase (SOD) in the liver and blood of rats accompanied by an increase in transaminases, bilirubin, and alkaline phosphatase. Treatment with carotenoids along with INH + RIF partially reversed lipid peroxidation, thiols, catalase, and SOD in the liver and blood of rats. Elevated levels of the enzymes in serum were also reversed partially by this treatment. The degree of necrosis, portal triaditis, and inflammation were also lowered in the carotenoids group. In conclusion, carotenoids supplementation in INH + RIF treated rats showed partial protection.

Endoplasmic Reticulum Stress Induced by Toxic Elements-a Review of Recent Developments.

Endoplasmic reticulum of all eukaryotic cells is a membrane-bound organelle. Under electron microscope it appears as parallel arrays of "rough membranes" and a maze of "smooth vesicles" respectively. It performs various functions in cell, i.e., synthesis of proteins to degradation of xenobiotics. Bioaccumulation of drugs/chemicals/xenobiotics in the cytosol can trigger ER stress. It is recognized by the accumulation of unfolded or misfolded proteins in the lumen of ER. Present review summarizes the present status of knowledge on ER stress caused by toxic elements, viz arsenic, cadmium, lead, mercury, copper, chromium, and nickel. While inorganic arsenic may induce various glucose-related proteins, i.e., GRP78, GRP94 and CHOP, XBP1, and calpains, cadmium upregulates GRP78. Antioxidants like ascorbic acid, NAC, and Se inhibit the expression of UPR. Exposure to lead also changes ER stress related genes, i.e., GRP 78, GRP 94, ATF4, and ATF6. Mercury too upregulates these genes. Nickel, a carcinogenic element upregulates the expression of Bak, cytochrome C, caspase-3, caspase-9, caspase-12, and GADD 153. Much is not known on ER stress caused by nanoparticles. The review describes inter-organelle association between mitochondria and ER. It also discusses the interdependence between oxidative stress and ER stress. A cross talk amongst different cellular components appears essential to disturb pathways leading to cell death. However, these molecular switches within the signaling network used by toxic elements need to be identified. Nevertheless, ER stress especially caused by toxic elements still remains to be an engaging issue.