In vitro induction of cytotoxicity and DNA strand breaks in CHO cells exposed to cypermethrin, pendimethalin and dichlorvos

The indiscriminate use of pesticides and herbicides to increase crop productivity has aroused a great concern among the environmental and health scientists due to their adverse effects in both target as well as non-target species. Although substantial information is available regarding their environmental and ecological impact, not much is known in regard to its toxicity in the mammalian system. Therefore a study was conducted for the assessment of cytotoxic and genotoxic effects of cypermethrin (Type II pyrethroid) dichlorvos (organophosphate) and pendimethalin (dinitroaniline herbicide) in Chinese hamster ovary (CHO) cells. CHO cells were exposed to 1 μM, 10 μM, 100 μM, 1000 μM, and 10,000 μM, cypermethrin, pendimethalin and dichlorvos for 3 h and cytotoxicity was assessed by MTT assay. Their genotoxic potential was also evaluated by Comet assay. The results demonstrate that dichlorvos and pendimethalin exhibited higher extent of cytotoxicity as compared to cypermethrin. A significant (p < 0.05) concentration dependent increase in DNA damage was observed with dichlorvos (0.01 μM and above) and pendimethalin (0.1 μM and above) as evident by Comet assay parameters viz., Olive tail moment (arbitrary units), tail DNA (%) and tail length (μM). Cypermethrin induced a significant (p < 0.05) DNA damage only at higher concentrations (1000 and 5000 μM). Our data indicates that these chemicals produce cytotoxicity and DNA damage in mammalian cells and should be used with caution.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Noninvasive recording of the His bundle electrogram in neonates

Summary Twenty-seven normal, nonsedated neonates had high-resolution electrocardiography performed during the first four days of life. Using high amplification, analogue and digital filters, and signal averaging, easily defined His bundle deflections of 0.75–7.75 (mean 2.5) V were detected in 25 (92.6%) of the 27 babies. The PH interval was 60–105 (mean 83) ms and the HV interval 10–25 (mean 17) ms. Surface His bundle electrocardiography is easily performed in the neonate and, as might be predicted, conduction intervals are considerably shorter than those seen in older age groups.A.W.N. and A.J.C. are supported by the British Heart Foundation.     

Transpupillary thermotherapy for retinal capillary hemangioma in von Hippel-Lindau disease

Retinal capillary hemangiomas are a common manifestation of von Hippel-Lindau disease. We report the treatment of a peripapillary retinal capillary hemangioma in the left eye of a 30-year-old woman with this condition, using infrared diode laser transpupillary thermotherapy (TTT). The hemangioma was evaluated before and after treatment by ophthalmoscopy, fundus fluorescein angiography, and Doppler ultrasonography. Infrared diode laser TTT was delivered over 3 sessions during a period of 22 weeks, resulting in an improvement in visual acuity from counting fingers to 6/24 and a marked decrease in exudates surrounding the hemangioma. Doppler ultrasonography demonstrated a decrease in intralesional blood flow from 7 cm per second to less than 3 cm per second, together with a decrease in the size of the lesion. Infrared diode laser TTT provides a useful modality in the treatment of retinal capillary hemangiomas, and may be particularly favorable for peripapillary lesions because of its relatively nondestructive characteristics.     

Kangaroo-related motor vehicle collisions

BACKGROUND: Motor vehicle collisions that are caused by large animals affect motorists in most parts of the world and tend to be increasing in incidence. Although traffic accidents involving kangaroos are common in Australia, we are not aware of any series that reported human injuries caused by such accidents. We aimed to study the mechanism, type, and outcome of these injuries. METHODS: Forty-six patients (32 male and 14 female patients; median age, 31.5 years) who presented to Royal Perth Hospital and who had been involved in a motor vehicle collision that was related to kangaroos between July 1994 and June 2000 were studied. RESULTS: The patients had a median Injury Severity Score of 9 (range, 1-41); 67.4% were car collisions and 32.6% were motorbike collisions, 41.3% had direct collision with a kangaroo, 34.8% hit a secondary object, and 32.6% rolled over. Most of these injuries affected the head and face (54.3%), upper extremities (57.4%), and lower extremities (40.4%). Only four had intracranial injuries (8.7%). Ninety percent of these collisions occurred at night, 74% in the countryside and 85% on highways or streets. The incidence was reduced during winter. Only one patient in this series died (2.2%). CONCLUSION: Most kangaroo-related motor vehicle collisions occurred at night, in the countryside, and on highways when the driver tried to avoid a kangaroo. Although injuries resulting from these collisions are relatively mild, increased awareness of their presence and ways to reduce them have to be promoted.     

Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression,superoxide dismutase and cytochrome P450 activity in rat brain

The antistress effect of bacosides of Brahmi (Bacopa monnieri, BBM), dissolved in distilled water, was -studied in adult male Sprague Dawley rats by administering oral doses of 20 and 40 mg/kg for 7 consecutive days. In half of the animals treated with 20 or 40 mg/kg of BBM, stress was given 2 h after the last dose. Stress was also administered to the animals treated with distilled water alone. BBM, at both doses, did not induce a significant change in the expression of Hsp70 in any brain region studied while stress alone produced a significant increase in the Hsp70 expression in all the brain regions. A significant decrease in the activity of superoxide dismutase (SOD) was evident in the hippocampus with the lower dose of BBM and in animals given stress alone, while an increase in the activity of SOD was observed in the brain regions with the higher dose of BBM. An increase in the activity of cytochrome P450 (P450) dependent 7-pentoxyresorufin-o-dealkylase (PROD) and 7-ethoxyresorufin-o-deethylase (EROD) was observed in all the brain regions after exposure to stress alone and with both doses of BBM although the magnitude of induction of P450 expression was less with a higher dose of BBM. Interestingly, stress when given to the animals pretreated with BBM for 7 days resulted in a decrease in Hsp70 expression in all the brain regions with a significant decrease occurring only in the hippocampus. Likewise the activity of SOD was found to be further reduced in all the brain regions in the animals treated with the lower dose of BBM followed by stress. However, when stress was given to the animals pretreated with the higher dose of BBM, a significant increase in the enzyme activity was observed in the cerebral cortex and in the rest of the brain while the activity of SOD was reduced to a much greater extent in the cerebellum and in the hippocampus. Likewise, the activity of P450 enzymes was found to be restored to almost control levels in the animals given stress and pretreated with the higher dose of BBM, while a lesser degree of induction, compared with animals treated with BBM or stress alone, was observed in the animals pretreated with the lower dose of BBM and given stress. The data indicate that BBM has potential to modulate the activities of Hsp70, P450 and SOD thereby possibly allowing the brain to be prepared to act under adverse conditions such as stress.     

The docking protein Gab2 is overexpressed and estrogen regulated in human breast cancer

Grb2-associated binder 2 (Gab2) is a recently identified member of the Gab/Daughter of sevenless family of docking proteins, which localize, amplify and integrate signaling pathways activated by various receptors including receptor tyrosine kinases (RTKs). To date, Gab2 signaling has been primarily investigated in hematopoietic cells. Here we report marked overexpression of Gab2 in a subset of breast cancer cell lines relative to normal breast epithelial strains and a trend for increased Gab2 expression in estrogen receptor (ER)-positive lines. Overexpression relative to normal ductal epithelium was also observed in some primary breast cancers. In MCF-7 breast cancer cells Gab2 was markedly tyrosine phosphorylated in response to heregulin and also following EGF, insulin or bFGF administration, indicating that a variety of RTKs implicated in breast cancer development or progression couple to this docking protein. In hormone-responsive breast cancer cells, GAB2 mRNA and protein expression were induced by estradiol in a manner sensitive to the pure anti-estrogen ICI 182780, indicating that this regulation is mediated via the ER. Gab2 therefore represents a novel link between steroid and growth factor signaling in breast cancer, and when overexpressed, may modulate the sensitivity of breast cancer cells to these important growth regulators.     

The bottom line: Outcomes after conservation treatment in anal cancer

At the Department of Radiation Oncology, Westmead Hospital, between 1980 and 2000, 60 patients with squamous cell carcinoma of anal canal or margin (including 15 with Stage IIIA or IIIB) were treated radically; 55 received chemoradiation (89% were prescribed mitomycin C and 5‐fluorouracil). Five‐year overall survival was 64% (95% confidence interval (CI): 48–79%), with a median survival of 9.75 years (median follow up 5.6 years, range 5 months to 22.5 years). Ten patients have died of disease. At 2 years the local control rate was 86%, and colostomy‐free survival was 83%. Relapse after 2 years was uncommon. Tumour size was the main factor driving outcomes, especially survival. Patients with larger tumours (T > 4 cm) had a hazard ratio for survival of 5.7 (95% CI: 1.8–17). Fourteen (24%) patients experienced treatment interruptions as a result of acute toxicity, including one death from neutropoenic sepsis. Seven (12%) patients, in total, experienced one or more late toxicities, grade 3 or above, including four women (all postmenopausal) who developed a radiation‐induced bone injury. Most patients with anal cancer can expect to retain a functional sphincter after chemoradiation/radiation. Further studies are in progress to determine the optimal chemoradiation protocol.     

Trisomy 21 with XYY

A case of double aneuploidy involving chromosome 21 and Y is reported in an eight-month-old infant with developmental delay and failure to thrive. Patient had all classical phenotypical features of trisomy 21 except, absence of epicanthal folds. The diagnosis was confirmed by cytogenetic study performed on peripheral blood leucocyte culture using G-banding. Literature review revealed only 17 cases of XYY and trisomy 21 reported so far. No such case is reported in Indian literature. Relevant literature is reviwed and possible effects of trisomy 21 on XYY and that of XYY on trisomy 21 has been discussed. A routine chromosomal study even in patient with classical features of Down syndrome has been advocated. Interestingly, our patient also had left to right shunts at atrial and ductal level and tricuspid regurgitation. Given the rarity of the disorder and scanty published data the incidence, phenotype and recurrence risk are difficult to establish.