Exploring miR-155-5p and miR-1246 as Diagnostic and Prognostic Markers in Oral Squamous cell carcinoma.

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is one of the leading cancers worldwide, significantly impacting developing nations. This study aimed to explore the diagnostic and prognostic potential of miR-155-5p and miR-1246 in OSCC in the Indian population, as their comparative roles in this context remain unexplored. MATERIAL AND METHODS: The present cross-sectional study comprised 50 histopathologically confirmed OSCC cases, with adjacent normal mucosa as controls. MiRNA expression was assessed via qRT-PCR and correlated with clinicopathological factors. MiRwalk and miRTargetlink were used for miRNA:mRNA interaction prediction, and gprofiler was employed to analyze validated targets for functional insights. RESULTS: The expression analysis showed a significant upregulation of miR-155-5p and miR-1246 in OSCC tissues compared to adjacent controls. Receiver operating curve analysis revealed that miR-1246 exhibited excellent diagnostic accuracy (AUC = 0.94) compared to miR-155-5p (AUC = 0.69). Higher miRNA levels were associated with age and extracapsular extension while overexpression of miR-1246 was correlated significantly with increased tumor size, tumor grade, TNM staging, and depth of invasion. The analysis for target prediction unveiled a set of validated targets, among which were WNT5A, TP53INP1, STAT3, CTNNB1, PRKAR1A, and NFIB. CONCLUSION: miR-155-5p and miR-1246 may be used as potential prognostic biomarkers in OSCC, with miR-1246 demonstrating superior diagnostic accuracy.

Effect of psychological stress on fertility hormones and seminal quality in male partners of infertile couples.

The present study evaluated the effect of psychological stress on male fertility hormones and seminal quality in male partner of infertile couples. Seventy male partners of infertile couples were evaluated for level of psychological stress using Hospital Anxiety and Depression Score (HADS) questionnaire, serum total testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) by electrochemiluminescence assay and serum GnRH by ELISA. Seminal analysis was performed as per WHO guideline. Nineteen (27%) of them had HADS anxiety and depression score ≥8 (abnormal HADS score). The persons having abnormal HADS had lower serum total testosterone, higher serum FSH and LH than those of persons having normal HADS. Serum total testosterone correlated negatively with HADS, but LH and FSH correlated positively. There was no change in GnRH with the change in stress or testosterone levels. Sperm count, motility and morphologically normal spermatozoa were lower in persons having abnormal HADS. Sperm count correlated positively with total testosterone and negatively with FSH and LH. Abnormal sperm motility and morphology were related to lower testosterone and higher LH and FSH levels. Psychological stress primarily lowers serum total testosterone level with secondary rise in serum LH and FSH levels altering seminal quality. Stress management is warranted for male infertility cases.

Hepatoprotective activity of six polyherbal formulations in paracetamol induced liver toxicity in mice.

BACKGROUND & OBJECTIVE: Polyherbal formulations available with a wide range of indications like protective to liver, appetite and growth promoters, gastrointestinal and hepatic regulator, as treatment for hepatic dysfunction, for hepatic regeneration as well as liver stimulant and tonic. Despite the widespread use, there is a lack of scientific evidence on their efficacy and safety. This study was undertaken to evaluate the hepatoprotective activity of six commercially available formulations, namely Liv 52, Livergen, Livokin, Octogen, Stimuliv and Tefroliv in acute liver toxicity in mice model induced by paracetamol (PCM). METHODS: Swiss albino mice of either sex were used, divided in 28 groups with six in each group. The dose of the polyherbal formulations was calculated from human dose (20 ml/day) using a standard conversion table. They were given as pretreatment (2.60 ml/kg/day) for 7 days by oral route twice a day prior to PCM administration. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg bw) on day 8. The study parameters were conducted on day 9. The biochemical parameters included liver enzyme levels alanine tranaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP). The pharmacological and pathological parameters were phenobarbitone sleeping time and macroscopic and microscopic changes of liver tissues respectively. RESULTS: PCM toxicity significantly increased ALT, AST and ALP (321.00 +/- 87.93, 273.17 +/- 45.68, 257.50 +/- 17.64 IU/l vs normal control, 33.33 +/- 0.61, 89.33 +/- 9.50, 152.17 +/- 11.40 IU/l respectively, P<0.05), prolonged phenobarbitone induced sleeping time (from 277.50 +/- 8.04 min to 335.83 +/- 7.00 min, P<0.05). When PCM higher dose (1g/kg p.o. single dose) was used, the liver tissue, in macroscopic appearance, showed extensive necrosis associated with haemorrhages. Low dose (500 mg/kg p.o. single dose) showed punctate haemorrhagic necrosis of liver tissue. In the microscopic studies, PCM induced toxicity showed haemorrhages, fatty changes and necrosis. The pretreatment in low doses (2.6 ml/kg/day) with liquid formulations of Liv 52 and Livergen reversed the PCM induced liver toxicity. At higher doses (5.2 ml/ kg/day), all the six herbal formulations conclusively showed marked beneficial effects in the studied pharmacological, biochemical and histological parameters. INTERPRETATION & CONCLUSION: The present findings demonstrated the efficacy of polyherbal liquid formulations at two dose levels in PCM induced hepatotoxicity in mice. However, it suggests that a dose adjustment may be necessary to optimize the effects in clinical settings.

Assessment of vagotomy status with postprandial urinary alkaline tide.

AIM: This study was carried out to assess whether the postprandial urinary alkaline tide, as a marker for the completeness of vagotomy, is dependent on the nature of the test meal, whether it is affected by proton pump inhibitor therapy, and whether it is reliable. METHODS: The postprandial urinary alkaline tide (PUAT) pattern was prospectively assessed in three different study groups and one control group of healthy volunteers. The three study groups were as follows; A (n = 20) i.e. the Proton Pump Inhibitor (PPI) Group; B (n = 25) i.e. the Truncal Vagotomy (TV) Group; and C (n = 5) i.e. the Recurrent Ulcer (RU) Group. Urinary pH was measured by a pocket digital pH meter. RESULTS: Postprandial urinary alkaline tide in the control group was significantly higher compared to the fasting levels. Liquid diet did not elicit a significant urinary alkaline tide response. There was a statistically significant fall in both fasting urinary pH (5.34 +/- 0.70 vs. 4.80 +/- 0.61, p = 0.031) and the postprandial alkaline tide (6.99 +/- 0.79 vs. 4.94 +/- 0.63, p = 0.0001) after taking proton pump inhibitors. In the truncal vagotomy and gastrojejunostomy group it was found that there was a significant fall in both the mean fasting (5.28 +/- 0.58, vs. 4.92 +/- 0.66, p = 0.032) and the postprandial urinary pH (6.29 +/- 0.92 vs. 5.09 +/- 0.73, p = 0.0001) following surgery. CONCLUSION: This study establishes that simple measurement of the urinary pH before and after a standard test meal can be used as an accurate routine test for the completion of vagotomy. It also showed that proton pump inhibitors abolish the alkaline tide and therefore must be discontinued before measuring the alkaline tide. Liquid test meal was not effective in eliciting an alkaline tide as compared to a solid meal.

Acute intermittent porphyria: diagnosis per chance.

OBJECTIVES: To report a case of acute intermittent porphyria (AIP) diagnosed by chance during routine investigations. CLINICAL PRESENTATION AND INTERVENTION: A 21-year-old female presented with vague gastrointestinal symptoms. Upon admission, she was disoriented. Later she developed generalized seizures and was treated with phenytoin, but the condition worsened. Upon investigation, her liver function, renal function, blood sugar level and electrolytes were within normal limits. When kept for routine laboratory testing, the color change in urine prompted us to investigate for porphyria. It was positive for phorphobilinogen (PBG) and urophorphyrin. Since AIP had been diagnosed, the initial treatment with phenytoin was discontinued with a favorable outcome. A screening test for PBG in urine by Ehrlich's reagent was performed on the patient's mother and was positive. CONCLUSION: A high degree of suspicion at the laboratory can also determine the diagnosis of AIP, which is often missed by the clinician.

OLR1 Gene Polymorphism and Oxidized LDL Levels in Metabolic Syndrome in Indian Population.

OBJECTIVE: Metabolic syndrome (MetS) is associated with abnormal lipid profile and high cardiovascular risk. There is an increased prevalence of coronary artery disease and Type 2 Diabetes Mellitus in India. Oxidized Low Density Lipoprotein Receptor 1(OLR1), a cell surface endocytosis receptor recognize, internalize and degrade oxidized LDL (oxLDL) in vascular endothelium and plays a role in the pathogenesis of atherosclerosis. The aim was to explore the association of OLR1 gene polymorphism and measure the serum levels of ox-LDL in patients with MetS in Indian population. MATERIALS AND METHODS: Forty cases fulfilling the IDF diagnostic criteria for MetS and 40 healthy controls having similar age and sex ratio were genotyped for OLR1 gene (SNP: IVS4-73C>T , rs3736234) by RFLP-PCR. Serum ox-LDL was estimated by ELISA.Their BP, BMI and waist circumference were measured. Fasting Plasma glucose, Serum Triglyceride and HDL-C were measured. RESULTS: Serum oxLDL was significantly higher in MetS cases as compared to controls (p < 0.0001). Odds ratio of T allele of above OLR1 SNP among subjects with MetS was 14.79 (95%CI: 1.80-121.2, p < 0.05). But no association was found between the SNP and serum ox-LDL levels. People having TT allele had higher BMI compared to those having CC allele. CONCLUSION: Ox LDL, being more atherogenic might contribute in the pathogenesis of MetS. The intronic SNP: IVS4-73 C>T of OLR1 gene increases the risk of developing MetS by a yet unknown mechanism that is independent of rise in ox-LDL. This OLR1 SNP probably influences BMI.

Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

BACKGROUND: Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. METHODS: Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. RESULTS: IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. CONCLUSION: Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

Hyperinsulinemia and dyslipidemia in non-diabetic benign prostatic hyperplasia.

BACKGROUND: BPH is a multifactorial disease. Several studies have elucidated the role of hormones and growth factors in its etiology. Insulin is a growth-stimulating hormone. Previous studies have reported the association between hyperinsulinemia, dyslipidemia and BPH in patients with metabolic disorders like diabetes. We evaluated insulin and lipid profile parameters in non-diabetic BPH cases and correlated it with prostate size. METHODS: 50 symptomatic BPH cases and 38 controls were included in this study. Fasting serum insulin concentrations were measured by radioimmunoassay. Insulin resistance was assessed by HOMA. Fasting glucose, total cholesterol and triglycerides were quantified by enzymatic methods. HDL-cholesterol was quantified by phosphotungstate magnesium chloride method. LDL-cholesterol was calculated by Friedwald's formula. RESULTS: Fasting serum insulin, HOMA, total cholesterol, and LDL-cholesterol were significantly higher and HDL-cholesterol was significantly lower in cases as compared to controls. Insulin was significantly associated with prostate size, cholesterol, triglycerides, VLDL-cholesterol and LDL-cholesterol in BPH cases. Stepwise regression analysis showed insulin as an independent risk factor in the development of BPH. CONCLUSIONS: Hyperinsulinemia associated with insulin resistance is an independent risk factor in the development of BPH.

Effect on gallbladder function subsequent to truncal vagotomy and gastrojejunostomy for chronic duodenal ulcer.

The effect of truncal vagotomy on gallbladder function and on the incidence of lithogenesis has remained controversial. A prospective and retrospective investigational study was undertaken to evaluate the effect of truncal vagotomy and gastrojejunostomy on gallbladder function. The study included a total of 76 patients and 77 controls. In Group I (Prospective group), 32 consecutive patients with chronic duodenal ulcer and gastric outlet obstruction undergoing truncal vagotomy and gastrojejunostomy were included. Group II included 25 age and gender matched controls (prospective group). Group III included 44 patients who had undergone truncal vagotomy and gastrojejunostomy 3 years or more prior to presentation (Retrospective group) and Group IV included 52 age and gender matched controls for the retrospective group. The patients in the prospective groups were followed up for a period of 1 year. An alkaline tide test was done in the prospective and retrospective group to assess for the completeness of vagotomy. Gallbladder contractile response to fatty meal and the presence of stones and sludge were noted in all the four groups by ultrasonography. There were 30 patients in the prospective group and 40 in the retrospective group after excluding patients with incomplete vagotomy. On ultrasound examination, there was no significant difference in the gallbladder volume and contractility of the study group when compared with the controls. Gallbladder sludge was found in 16 to 25% of patients in the prospective group (group I) during follow up, where as similar finding was documented in 8% of the matched control (group II (P>0.1). However, in the retrospective (group III) 10% (4 out of 40) had calculi and 20% of patients demonstrated sludge which was significantly higher when compared with the controls (p = 0.001). Truncal vagotomy and gastrojejunostomy did not affect gallbladder contractility, but it might predispose to the formation of sludge and subsequent calculi in a proportion of patients in long term.

Does vitamin D mediate inhibition of epithelial ovarian cancer by modulating cytokines?

OBJECTIVE: Vitamin D deficiency is reported to be involved in pathogenesis of ovarian cancer. But the mechanism is yet to be explored. An imbalance between Th1 and Th2 activity play a crucial role in pathogenesis of many cancers. The purpose of the study is to find out the Th1/Th2 status by estimating TNF-α (Th1 marker) and IL-4 (Th2 marker) in ovarian cancer cases and controls and to correlate these with serum vitamin D levels. MATERIALS AND METHODS: A case-control study with 50 ovarian cancer cases and 50 healthy controls was conducted. The cytokines TNF-α and IL-4 were estimated by ELISA. Serum vitamin D was measured by electro-chemiluminescence immunoassay method. RESULTS: Median TNF-α levels (12.2 vs 6.2 pg/ml; p value <0.001) were significantly higher in ovarian cancer patients and mean IL-4 levels (2.22 ± 0.51 vs 2.99 ± 0.68 pg/ml; p value <0.05) were significantly lower as compared to those of controls. Levels of TNF-α and IL-4 did not vary significantly with clinical staging, and histological grading. Vitamin D levels were negatively correlated with TNF-α and positively correlated with IL-4. CONCLUSIONS: Low vitamin D levels promotes Th1 activity increasing TNF-α levels and inhibits Th2 activity decreasing IL-4 levels in ovarian cancer. These low levels of vitamin D may induce pro-inflammatory micro ambience which might contribute to pathogenesis of ovarian cancer.

Platelets from eclampsia patients have reduced membrane microviscosity and lower activities of the signalling enzymes.

It has been shown that platelets from patients suffering from eclampsia are hyporesponsive to stimulation by agonists like thrombin and ADP. Although platelet hyporeactivity contributes to the pathogenesis of the disease process, the cause for this is still not known. Platelet aggregation and secretion are membrane-based phenomena initiated by the processes of cell signalling. Hence, to understand the mechanisms underlying platelet hyporeactivity in eclampsia, membrane microviscosity and activities of the signalling enzymes were measured in human platelets stimulated with thrombin. Membrane fluidity was determined from the steady-state fluorescence anisotropy of diphenylhexatriene incorporated in cell membranes. Activities of phospholipase C and protein kinase C in stimulated platelets were assessed from the extents of phosphatidic acid generation and pleckstrin phosphorylation, respectively. Platelet membrane microviscosity in eclampsia (2.3 +/- 0.2 SEM, n = 5) was significantly lower (P < 0.05) than that in the matched gravid control subjects (3.1 +/- 0.2, n = 4). In eclampsia, generation of phosphatidic acid and phosphorylation of pleckstrin were decreased by 25% (P < 0.05, n = 3) and 35% (P < 0.05, n = 3), respectively, after 60 sec of platelet stimulation. It was concluded that the hyporeactive platelets obtained from eclampsia have more fluid membranes and diminished activities of phospholipase C and protein kinase C. In summary, this study shows that alterations in membrane fluidity and activities of the signalling enzymes (phospholipase C and protein kinase C) may contribute to the diminished platelet responsiveness observed in the eclamptic condition.

Effects of in-vivo generation of oxygen free radicals on immune responsiveness in rabbits.

Oxygen free radicals (OFRs) generated during biological processes are reportedly involved in the pathogenesis of several disease states and various reports have indicated that oxidative stress may alter immune competence. Hence, effects of in-vivo generation of OFRs by using xanthine/xanthine oxidase (X/XO) system on immune responsiveness were evaluated in rabbits. Intravenous injections of xanthine (0.14 mg/kg) along with xanthine oxidase (2 U/Kg) following primary and secondary immunizations of animals with sheep red blood cells (SRBC) significantly attenuated the primary and secondary antibody responses respectively. In tests for cell-mediated immunity, tuberculin sensitivity and leucocyte migration inhibition were also decreased significantly in sensitized animals following X/XO treatment. The observed changes in both humoral and cell-mediated immune responses following such in-vivo generation of OFRs indicate a possible nexus between OFR generation and immune suppression.

Evaluation of new WHO diagnostic criteria for diabetes on the prevalence of abnormal glucose tolerance in a heterogeneous Nepali population--the implications of measuring glycated hemoglobin.

AIM OF THE STUDY: The present study was designed to (a) evaluate the implications of revised WHO diagnostic criteria on prevalence of abnormal glucose tolerance, (b) compare glycated hemoglobin level amongst healthy, impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and diabetic subjects and (c) evaluate the assay of glycated hemoglobin in screening IGT, IFG from normal subjects. METHODOLOGY: Hospital based, cross-sectional study. Plasma glucose and glycated hemoglobin (gHb) were estimated by glucose oxidase and affinity chromatography method respectively. RESULTS: The crude prevalence of IFG, IGT and diabetes were 9%, 18% and 5.29% respectively with no significant difference between Mongol and non-Mongol population. Newly introduced IFG group falsely incorporate 12% diabetic subjects and fails to detect 83% IGT subjects as impaired glucose metabolism. The gHb level is raised in IGT and diabetic group but not in IFG group. CONCLUSION: The assay of gHb may be used to screen abnormal glucose tolerance but paired estimation of fasting glucose increases the reliability of diagnosis. The level of gHb in mild carbohydrate intolerance mostly depend on the level of rise in post prandial glucose (where the variation is wide, as in IGT) but not on the narrow variance in fasting plasma glucose level as found in IFG.

Diagnostic peritoneal lavage (DPL)--is it useful decision making process for management of the equivocal acute abdomen?

Patients with a traumatic or non-traumatic acute abdominal conditions often have equivocal findings regarding the need for surgery. Ultrasound and computed tomography, though useful, have limitations and not always available in peripheral hospitals. Diagnostic peritoneal lavage (DPL) was investigated as an aid to decision-making in such patients. After preliminary X-ray and ultrasound, DPL was performed in 50 patients with an equivocal acute abdomen (18 trauma, 32 non-trauma). It was found that overall sensitivity, specificity, accuracy, and positive and negative predictive values were high for patients with trauma. All the above parameters except specificity and negative predictive value (NPV) were also found to be high for the non-trauma group. DPL was found to be a bedside investigation, which helped in taking the decision to operate on patients with both traumatic and non-traumatic acute abdomen.

Thyroid dysfunction in eastern Nepal.

Nepal lies in an area of endemic iodine deficiency. Thyroid dysfunction, along with a higher than average prevalence of goiter, is a major public health problem among the local population. The present study was undertaken to investigate the prevalence of thyroid dysfunction among the hill and terai (low land) castes of eastern Nepal that attended the thyroid clinic at the BP Koirala Institute of Health Sciences (BPKIHS), Dharan. A total of 599 cases were studied during a single year. The distribution of hyperthyroid and hypothyroidism was 13.68% and 17.19% respectively. The majority of the thyroid dysfunction was seen in the 21-40 year age group. The prevalence of hypothyroidism was slightly higher among terai castes (17.66%) when compared with hill castes (15.17%). There was a similar distribution of thyroid dysfunction among the male and female populations of the goitrous subjects (n=157), most were euthyroid (58.59%); hyperthyroidism affected (27.38%). Since, it was a hospital-based study, the prevalence of thyroid dysfunction may not be applicable to the general population. Extensive field-based countrywide epidemiological studies are necessary to provide data about thyroid dysfunction in the community.

Assay of iodine deficiency status in three ecological regions of Nepal by a microdigestion method.

Iodine deficiency disorders (IDD) are a global public health problem. In continuation of the efforts to eliminate the iodine deficiency in different parts of the world, IDD surveys are being conducted to assess the status of iodine nutriture. A survey was conducted in Nepal in 1998 with assistance from UNICEF. We present the status of the iodine nutriture, as assessed from urinary iodine levels of casual samples by a micro-digestion method, in the three ecological regions: Terai (flat region), Hilly region (300-3,000 m altitude) and mountainous regions (>3,000 m altitude) of Nepal. Terai region is more affected, having iodine deficiency in 18.6% of the population. The hilly and mountainous regions were found to have 11.2% and 9% iodine deficient populations respectively. The study shows improvement in iodine deficiency status with respect to previous surveys yet it continued to be prevalent in the country as a major public health problem which requires strengthening of preventive measures.

Prevalence of non-insulin dependent diabetes mellitus in urban areas of eastern Nepal: a hospital based study.

Non-insulin dependent diabetes mellitus (NIDDM), which affects millions of people throughout the world, is a widely prevalent chronic debilitating disease that causes short term and long term complications. It is a problem in a developing country like Nepal, where there has been no report of prevalence. Hence this study was undertaken to investigate the prevalence of NIDDM among urban patients attending the outpatient clinic of BP Koirala Institute of Health Sciences (BPKIHS) hospital, and coming from the eastern part of Nepal. A sample of 1,840 subjects was incorporated in the study during a period of one year. WHO diagnostic criteria (1985) were followed to establish the diagnosis of NIDDM. The prevalence of diabetes was 6.3% (1.63% previous and 4.67% new) which is relatively high in comparison to many other countries. The prevalence of NIDDM in females was relatively lower (5.75%) than in males (6.73%). The prevalence showed an increasing trend with increasing age. The high incidence (new cases) of NIDDM in Nepal as found in the study may be due to lack of public awareness regarding the problem and poor medical services in the country.

Effects of stress on gamma glutamyl transpeptidase (GGT) activity in lymphoid system of rats: modulation by drugs.

Effects of stress and its modulation by adaptogens were evaluated on gamma glutamyl transpeptidase (GGT) activity in different tissues of the lymphoid system in rats. Restrain stress (RSx5) suppressed the GGT activity in different tissues of lymphoid system viz. the lymphocyte, the spleen, the thymus and the macrophage, and the maximum effect was seen in the spleen. Chlordiazepoxide, a prototype anti-stress agent, which did not alter GGT activity per se, reversed the effect of RS on this enzyme activity in tissues of lymphoid system studied. Azardirachta indica (Al, Neem), an indigenous adaptogen stimulated the GGT activity per se and nearly normalised RS induced suppression of GGT in lymphoid system. The observed suppression of GGT activity in lymphoid system by stress and its modulation by natural and synthetic adaptogens indicates that GGT could be a consistent cellular/biochemical marker of stress responsiveness and stress-induced immunomodulation.

Immunotoxicity of pesticides: perspectives and trends.

In recent years, great concern has been expressed about genotoxic potential of pesticide chemicals. These toxic chemicals have become an integral part of the ecosystem and the human health effects of these agents are yet to be satisfactorily defined. The objectives of this review is to examine the sources of information available; evaluation of experimental protocols employed for assessment of immunological effects; and to study specific cellular and molecular locus which could be responsible for impaired immune responsiveness. It is emphasized that threshold level for the pesticide effect below which no effect would be seen, depends on the animal species, the method of testing for immune responses and type of antigen used. A comparative assessment of immune responses using different antigens is, therefore, an important aspect of pesticide immunotoxicity. In view of widespread use, distribution and stability of some of these compounds in the environment, pesticide exposure may play a greater role in suspected fragile immune system, and may result in altered disease susceptibility. An understanding of these risks depends, to a great extent, upon cellular and molecular events underlying pesticide-induced immune alterations in experimental animals. It is, therefore, proposed that pesticide chemicals may influence humoral immunity while having no detectable effect on cell-mediated immunity (CMI); immune dysfunction is related to dose and duration of pesticide exposure; a single assay of immune function may not be appropriate to detect pesticide-induced immune dysfunction; since many immune responses are genetically controlled, alterations in responsiveness to one challenge in a given animal model may not hold true in second one; although it has been established that pesticide chemicals can alter immune function, the mechanisms of action have yet to be determined. This paper also reviews the effects of pesticide on lymphocyte function and suggests that lymphocyte dysfunction may be an integral part of pesticide-induced immunosuppression and presents an approach which may serve to delineate the possible mechanisms of action. It is quite clear that pesticide-induced immunomodulation endangers humans and animals. This hazard should, therefore, not to be underestimated in evaluation of toxicity of these chemicals. However, additional research is needed in basic mechanism of immunotoxicity and identification of susceptibility factors which predispose to these reactions.

Modulation of gamma glutamyl transpeptidase activity in lymphoid system by organochlorine pesticides in rats.

Effects of 1,1,1,-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) and lindane were studied on gamma glutamyl transpeptidase (GGT) activity in different tissues of the lymphoid system in rats. DDT (100 or 200 ppm) and lindane (30 or 80 ppm) exposure for 8 weeks suppressed the GGT activity in a dose dependent manner in thymus and macrophage. In spleen, significant decrease in the enzyme activity was observed at higher exposure (200 ppm DDT or 80 ppm lindane) levels. Lindane suppressed GGT activity at both 30 or 80 ppm dose levels, while DDT reduced the GGT activity at 200 ppm but not at 100 ppm exposure in lymphocyte. The study indicates the possibility of using GGT as an effective and consistent biochemical marker for immunotoxicity of xenobiotics and other environmental stressors.