Apolipoprotein E polymorphism and its relation to plasma lipids in coronary heart disease.

Background : The present investigation is aimed at examining the Apolipoprotein E (APOE) genotypic influence on coronary heart disease (CHD) risk in northwest India (Punjab), where this disease is emerging as a major threat to public-health care system. Materials and Methods: The present study comprised of angiographically diagnosed coronary heart disease patients (n = 193) and controls (n = 150) of Punjab. Genetic polymorphism of APOE gene was investigated by polymerase chain reaction (PCR), and its association with lipid levels was evaluated. Results : The allele frequencies of epsilon2, epsilon3, and epsilon4 were 0.054, 0.795, 0.151; and 0.077, 0.856, 0.067 in patients and controls respectively. The bearers of E3/E4 genotype had threefold higher propensity of developing CHD in this population (OR, 3.04; CI, 1.55-6.25; P P P Conclusions : A significant association (P = 0.016) of epsilon4 allele, especially E3/E4 genotype, with CHD was observed, along with HDL-C and LDL-C concentrations, in the population of northwest India.

Role of enteric fever in ileal perforations: an overstated problem in tropics?

PURPOSE: To determine the role of enteric fever in ileal perforations. METHODS: A prospective cohort of 47 patients of ileal perforation was subjected to clinical examination and investigations for APACHE II scoring. Blood, ulcer edge biopsy, mesenteric lymph node and peritoneal aspirate were subjected to culture to determine the predominant aerobic bacterial isolate and its antibiogram. RESULTS: Seven patients (14.9%) required intensive care and seven (14.9%) developed septicaemia. Mortality was 17%. Highest isolation rate was seen in ulcer edge (70.2%) followed by lymph node (66%) culture. The bacterial spectrum was Escherichia coli (23.4%), Enterococcus faecalis (21.3%), Salmonella enterica serovar Typhi (6.3%), Salmonella enterica serovar Paratyphi A (4.2%), etc. CONCLUSIONS: Enteric fever organisms are not the predominant causative agents of ileal perforations. Culture of ulcer edge biopsy, lymph node is crucial for aetiological diagnosis. The use of APACHE II triaging and prescription of antimicrobials based on the local pattern of susceptibility profile of the aetiological agent is recommended.

Malaria control using deltamethrin impregnated mosquito nets/ insecticide treated bed nets: experience in armed forces.

The study was undertaken to evaluate the impact of deltamethrin-impregnated mosquito nets on malaria incidence, mosquito density, any adverse side effect among users. A field trial was carried out over a period of three years in two adjacent military stations at Allahabad (UP), keeping one as a trial and other as a control station. During first year, baseline data were collected and during next two years residual spray was replaced with use of deltamethrin impregnated mosquito nets in trial station. The use of deltamethrin-impregnated mosquito nets/insecticide treated bed nets resulted in a significant decline in malaria incidence and Annual Parasite Index (API). The average mosquito density of Anopheline mosquitoes decreased by 67.8% and Culex by 49.7%. The insecticide was found safe for use amongst troops. Use of deltamethrin-impregnated mosquito nets has beneficial impact on integrated control of malaria.

Malaria control using deltamethrin impregnated bed nets in a cantonment area at Allahabad (U. P.).

The study was undertaken to evaluate the impact of deltamethrin impregnated mosquito nets on malaria incidence, mosquito density, any adverse side effect among users and collateral effects on bed bugs and houseflies. A field trial was carried out over a period of three years in two adjacent military stations at Allahabad (UP), keeping one as a trial and other as a control station. During first year, baseline data were collected and during next two years residual spray was replaced with use of deltamethrin impregnated mosquito nets in trial station. The use of deltamethrin-treated bed nets resulted in a significant decline in malaria incidence and annual parasite index (API). The average mosquito density of anopheline mosquitoes decreased by 67.8% and culicine by 49.7%. The insecticide was found safe for use amongst troops and had favourable collateral effects against bed bugs and flies. Use of deltamethrin impregnated bed nets has beneficial impact on integrated control of malaria.

Metaplastic carcinoma of the breast--a rare breast tumour.

Malignant breast neoplasms consisting of mixtures of epithelial and mesenchymal elements, are a rarity. Pathogenesis of such diverse elements within obviously infiltrating carcinomas has been the subject of much controversy. After the advent of immunohistochemistry, it is now generally accepted that metaplasia of the epithelial elements of a carcinoma gives these lesions their pseudosarcomatous appearance. Hence the name metaplastic carcinoma is given to malignant breast neoplasms which show Cytokeratin positivity in both epithelial and mesenchymal elements. We recently encountered such a case, which is being presented here along with relevant review of literature.

Study of events leading cellular senescence to human mammary epithelial cancer cells in vitro.

Role of various growth regulatory factors in inducing senescence in cultured HMEC cells have been investigated in ten cases of breast cancer. The histological grade of tumour cells is found to play significant role in controlling the proliferation and phenotypic charateristics of cultured HMEC cells during primary culture and also number of subsequent passages resulting in complete cellular senescence in them. Effects of conditioned media (CM) collected from primary and senescent cultures of these HMEC cells had also been studied on proliferation of their own HMEC cells used as target cells, to evaluate the role of various autocrine growth factors produced by them. Significant increase in proliferation of target cells was noticed on their exposure to CM from senescent cultures, while cessation of their proliferation was found on their exposure to CM from senscent cultures, suggesting that HMEC cells produce growth promoting factors during primary culture and growth inhibitory factors on subsequent passages, responsible for inducing features of cellular senescence in them. The role of epidermal growth factors (EGF) and transforming growth factors (TGF) alpha and beta as autocrine factors in inducing senescence of cultured HMEC cells were also investigated. Deletion of EGF from growth media initially caused decreased proliferation to target HMEC cells, followed by improvement in their proliferation. Supplementation of growth media by TGF-alpha induced significant increase in proliferation of target cells. Addition of epidermal growth factors receptor (EGFR) antibody to cells exposed to media devoid of EGF and media supplemented with TGF-alpha showed marked suppression of proliferation of target cells. The morphologic and phenotypic characteristics of target HMEC cells exposed to TGF-alpha were also found similar to those HMEC cells grown during primary culture, suggesting autocrine production of EGF and TGF-alpha by cultured HMEC cells during primary culture. Supplementation of TGF-beta to growth media induced marked suppression of proliferation to target cells along with morphologic and phenotypic features of terminal differntiation or senescence. Exposure of senescent cells to media supplemented with EGF and TGF-alpha could not induce their proliferation. This suggest that HMEC cells on subsequent passages undergo some genetic and phenotypic alterations resulting in production of growth inhibitory factor like TGF-beta which induces cessation of their proliferation alone with features of senescence.

Fine needle aspiration cytology, histology and MIB-1 proliferative index in a case of dyshormonogenetic goitre.

The fine needle aspiration (FNA) cytologic findings along with histology and MIB-1 proliferative index in a case of dyshormonogenetic goitre is presented. A 12-year old female child from non-endemic zone presented with a isotopically cold solitary thyroid nodule with a history of goitre being present since birth. Past history of any neck irradiation or maternal ingestion of any goitrogen during the antenatal period and family history of goitre were negative. FNA cytology revealed an extremely cellular preparation with predominantly microfollicular pattern without colloid. Nuclei were round to oval, slightly enlarged with evenly distributed chromatin and inconspicuous nucleoli. Larger tissue fragments also showed foci of solid cell groups with nuclear crowding, overlapping and loss of polarity in addition to the prevalent microfollicular pattern. Occasional tissue fragments showed solid groups of trapped follicular epithelial cells in the matrix of fibrocollagenous tissue. Histology showed an intensely hyperplastic follicular cells with nodule formation, irregular fibrosis, pseudo capsular or vascular wall invasion mimicking malignancy. Immunohistochemistry for calcitonin was negative but thyroglobulin was positive. MIB-1 (Ki-67) proliferation index varied from 0.05 to 0.26 (mean 0.13) in the hyperplastic nodules versus 0.9 to 2.1 (mean 1.34) in the hyperplastic solid microfoci scattered amidst the grossly normal appearing thyroid tissue. The possible cytologic diagnostic pitfalls in favor of follicular neoplasm is discussed.

Hepatic and renal oxidative stress in acute toxicity of N-nitrosodiethylamine in rats.

Nitrosoamines such as N-nitrosodiethylamine (NDEA) produce oxidative stress due to generation of reactive oxygen species and may alter antioxidant defence system in the tissues. NDEA was administered ip as a single dose to rats in LD50 or in lower amounts and the animals were sacrificed after 0-48 hr of treatment. The results showed that lipid peroxidation in liver increased, however no significant increase in kidney LPO was observed after NDEA administration. Superoxide dismutase (SOD) and glutathione reductase (GSH-R) activity increased in liver, however, catalase (CAT) activity in liver was inhibited in NDEA treated rats. Kidney showed an increase in SOD activity after an initial decrease along with increase in GSH-R activity in NDEA treated rats. However, kidney CAT activity was not significantly altered in NDEA intoxicated rats. Serum transaminases, serum alkaline phosphatase blood urea nitrogen, serum creatinine and scrum proteins were elevated in NDEA treated rats. The results indicate NDEA-induced oxidative stress and alteration in antioxidant enzymes in liver and kidney to neutralise oxidative stress.

Coronary stenting in diabetics: six months clinical and angiographic outcome.

The aim of this study was to assess the clinical and angiographic outcome of coronary stenting in diabetics as compared to non-diabetic patients. A total of 114 patients undergoing coronary angioplasty with stenting were prospectively evaluated. There were 30 diabetic (group A) and 84 non-diabetic (group B) patients. There were no significant differences in both the groups with respect to other risk factors and clinical characteristics. Both the groups were also comparable in terms of lesion morphology and stent types. The clinical endpoints were recurrent angina, reinfarction, cardiac death and need for target vessel revascularisation. The angiographic endpoint was angiographic restenosis at six months. There were 70 males and 44 female patients with a mean age of 55 +/- 12 years. Angiographic follow-up was completed in 85 (74.7%) patients which included 25 (83.3%) patients in group A and 60 (71.4%) in group B. Among clinical events at 30 days, the incidence of recurrent angina was 10.0 percent versus 8.3 percent (group A and B; p = NS) and incidence of reinfarction was 6.6 percent versus 5.9 percent (group A and B; p = NS), respectively. At six months, recurrent angina was seen in 16.6 percent versus 15.4 percent (p = NS) and reinfarction was seen in 10.0 percent versus 8.3 percent (p = NS) in group A and B, respectively. There were no deaths in either group. The angiographic restenosis rate was significantly higher in diabetics compared to non-diabetics (40.0% vs 23.3%; p = 0.02). The need for target vessel revascularisation was higher in diabetics as compared to non-diabetics (16.0% vs 6.6%; p = 0.03). We conclude that in spite of using coronary stents, the diabetics have higher restenosis rate and higher target vessel revascularisation rate than the non-diabetic patients.

Lipid peroxidation and antioxidant enzymes in isoproterenol induced oxidative stress in rat erythrocytes.

Isoproterenol, upon oxidation, produces quinones which react with oxygen to produce superoxide anions (O2.-) and H2O2. In the present study, isoproterenol was administered to rats in two doses so as to evaluate its beta adrenergic and toxicological action in terms of lipid peroxidation (LPO) and antioxidant enzymes in erythrocytes. Isoproterenol (30 mg/100 g body wt.) was administered to rats and the animals were followed up to 7 days after administration. Some of these animals were treated with a second dose of isoproterenol 24 h after the first dose and the animals were followed up to 12 h. The result showed increased lipid peroxidation (LPO) and superoxide dismutase (SOD) activity in erythrocytes in response to isoproterenol. Catalase (CAT) activity in erythrocytes decreased with isoproterenol between day 2-7 as compared to control. The second injection of isoproterenol showed increased CAT activity in erythrocytes which decreased at 12 h as compared to control. The erythrocyte GSH content and glutathione-S-transferase (GST) activity decreased with isoproterenol treatment as compared to control. However, erythrocyte GSH content as well as GST activity both recovered towards control with time. Elevated serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and glutamate oxaloacetate transaminase (GOT) activity was observed after isoproterenol treatment. The results show increased LPO and altered antioxidant system in erythrocytes in response to isoproterenol induced oxidative stress.

Hyalinizing trabecular adenoma--a case report with FNAC histologic, MIB-1 proliferative index and immunohistochemical findings.

Hyalinizing trabecular adenoma is a recently described benign thyroid tumor, almost exclusively occurring in females. The morphological features of this entity overlap with both papillary and medullary carcinoma to varying extent. This, in turn, creates a situation of serious diagnostic pitfall particularly for a false positive diagnosis of papillary carcinoma in fine needle aspiration (FNA) cytology. False consideration of medullary carcinoma is also possible by the unwary especially if staining for Congo red and/or immunostaining for calcitonin is not resorted to. At histologic level, the distinctive architectural pattern is however of great help and thus poses a much lesser danger of misdiagnosis. We relate here our experience in a recently encountered case of hyalinizing trabecular adenoma and describe detailed FNA cytologic and histologic findings along with immunohistochemical profile using a panel of eight monoclonal antibodies. The tumor proliferative potential has also been assessed using MIB-1 (Ki-67) immunostaining. The various pros and cons of diagnostic pitfalls are discussed.

Lipid peroxidation and antioxidant enzymes in erythrocytes and tissues in aged diabetic rats.

Antidiabetic treatment with powdered fruit of Capparis decidua decreased alloxan induced lipid peroxidation (LPO) significantly in erythrocytes, kidney and heart. Erythrocyte superoxide dismutase (SOD) activity decreased while the kidney and heart SOD increased in diabetic animals. These alterations in SOD were counteracted by insulin as well as with powdered fruit of C. decidua. Increased catalase (CAT) activity in erythrocytes, liver, kidney and heart with C. decidua treatment indicate that the treatment may neutralize H2O2 toxicity by its increased decomposition by CAT. Result shows that treatment with C. decidua lowers alloxan induced LPO and alters SOD and CAT enzymes to reduce oxidative stress.

Protective effect of glutathione and selenium against alloxan induced lipid peroxidation and loss of antioxidant enzymes in erythrocytes.

Alloxan is a diabetogenic drug and is known to induce diabetes through generation of free radicals. The toxic oxygen species can be detoxified by antioxidant enzyme system and thus reduce the deleterious effect of lipid peroxidation. Erythrocytes exposed to alloxan induced lipid peroxidation in vivo as well as in vitro. Although alloxan treatment produced a deleterious effect on antioxidant enzymes, pretreatment with glutathione and selenium led to a recovery of the activities of superoxide dismutase and glutathione peroxidase. However, catalase activity increased on alloxan treatment. Alloxan reduced blood glucose level significantly within 60 min but thereafter a slow and steady rise was observed.

Photoprotection of ultraviolet light irradiated E. Coli. B/r cells.

Ultraviolet irradiated E. Coli. B/r cells recover from UV damage when the cells are kept in dark due to dark repair mechanism. Photoprotection by illumination of the cells in near UV light prior to the exposure to UV light increases the capacity of the cells to induce L-arabinose isomerase synthesis in response to inducer, L-arabinose. The survival of the cells is dependent on the UV dose. The increased synthesis of L-arabinose isomerase after photoprotection is due to the amount of cyclic AMP in the cells.

Zinc protection against lipid peroxidation from cadmium.

Effect of zinc and cadmium on lipid peroxidation and catalase activity in liver, heart, brain and testis was determined in order to characterise the interaction of zinc with cadmium. Zinc and cadmium both increased lipid peroxidation significantly in the tissues studied. In animals pretreated with zinc prior to cadmium administration, significant decrease in lipid peroxidation in liver was observed. Lipid peroxidation was not affected significantly in testis but a significant increase was observed in heart and brain tissues. Catalase activity in testis increased significantly by zinc treatment with or without cadmium administration.