Epidemiology of abnormal uterine bleeding

Menstrual dysfunction is a common cause of referral to the gynaecology clinic, and the problem has a considerable impact on the health status and the quality of life of women. The aetiology is varied and the burden on the healthcare system continues to grow. There is an urgent need for clinicians to develop effective preventive strategies and treatment modalities that can be available to women in the community.     

Intradialytic hypotension and vascular access thrombosis

Identifying potential modifiable risk factors to reduce the incidence of vascular access thrombosis in hemodialysis could reduce considerable morbidity and health care costs. We analyzed data from a subset of 1426 HEMO study subjects to determine whether more frequent intradialytic hypotension and/or lower predialysis systolic BP were associated with higher rates of vascular access thrombosis. Our primary outcome measure was episodes of vascular access thrombosis occurring within a given 6-month period during HEMO study follow-up. There were 2005 total episodes of vascular access thrombosis during a median 3.1 years of follow-up. The relative rate of thrombosis of native arteriovenous fistulas for the highest quartile of intradialytic hypotension was approximately twice that of the lowest quartile, independent of predialysis systolic BP and other covariates. There was no significant association of intradialytic hypotension with prosthetic arteriovenous graft thrombosis after multivariable adjustment. Higher predialysis systolic BP was associated with a lower rate of fistula and graft thrombosis, independent of intradialytic hypotension and other covariates. In conclusion, more frequent episodes of intradialytic hypotension and lower predialysis systolic BP associate with increased rates of vascular access thrombosis. These results underscore the importance of including vascular access patency in future studies of BP management in hemodialysis.     

Interobserver variability in the assessment of clinical criteria for suspected urinary tract infection in nursing home residents.

We determined the interobserver variability in the assessment of clinical criteria for urinary tract infection (UTI) in nursing home residents. Pairs of nursing home staff caring for 30 residents were interviewed at the time UTI was suspected. At least one measure from each of 7 clinical criteria categories was reliably assessed by nursing home staff members.     

A facile and new approach to synthesize 2-amino-4-(4-amoinophenyl)-1<Emphasis Type="Italic">H</Emphasis>-1,3-diazol-1-yl-alkylaminomethanethiones

An “intellectual connection” approach to design a facile and new synthesis of suitably substituted 2-aminoimidazole-based precursors of expected antiasthmatic agents through a benzidine type of rearrangement of 2-phenylazoimidazole and subsequent coupling of the product thus obtained with alkylisothiocyanates involving a degenerative operation, thereby improving the time frame of the overall synthetic sequence, is reported. The alkylisothiocyanates required in this synthetic sequence are prepared using a best combination of reported methods. The compounds reported here can be used to produce derivatives of other biological agents.     

Lead induced oxidative damage and its response to combined administration of alpha-lipoic acid and succimers in rats

Alpha-lipoic acid (LA) has been reported to be highly effective in improving the thiol capacity of the cells and in reducing lead induced oxidative stress. These results suggested its possible role as a therapeutic intervention of lead poisoning in combination with a chelator. We investigated the effects of LA, either alone or when administered in combination with succimer (meso 2,3-dimercaptosuccinic acid; DMSA or one of its analogue monoisoamyl DMSA), in influencing the lead induced alterations in haem synthesis pathway, hepatic, renal and brain oxidative stress and lead concentration from blood and soft tissues. The results suggest a significant lead induced inhibition of delta-aminolevulinic acid dehydratase (ALAD), reduction in glutathione (GSH) and an increased zinc protoporphyrin (ZPP) level in blood, indicating altered heme synthesis pathway. Both the thiol chelators were able to increase blood ALAD activity and GSH level towards normal. The most prominent effect on blood ALAD activity was however observed when monoisoamyl DMSA (MiADMSA) was co-administered with LA. Lead exposure produced significant depletion of hepatic GSH, while, oxidized glutahione (GSSG), thiobarbituric acid reactive substances (TBARS) and catalase activity increased significantly, suggesting hepatic oxidative stress. All the treatments were able to increase hepatic GSH and reduce GSSG levels, while, TBARS level reduced significantly in animals administered LA and MiADMSA, individually or in combination. Lead induced increase in renal GSSG, TBARS levels and catalase activity, were effectively reduced by LA, while, the two chelators when administered alone were effective only in reducing GSSG and catalase activity. The most prominent beneficial effects, however, were observed in animals treated concomitantly with LA and one of the chelators (DMSA or MiADMSA). Brain GSH and GSSG levels decreased moderately while superoxide dismutase (SOD) activity remained statistically unaltered on lead exposure. Brain catalase activity, on the other hand, increased significantly. Administration of LA was effective in reducing these alterations in the brain, however, the best effects were achieved in animals co-administered LA and one of the thiol chelators. The results point to a significant beneficial role of LA in the recovery of altered biochemical variables both during monotherapy and when given in combination with succimer. It however, showed no chelating properties in decreasing lead burden from blood, liver and kidneys except for a significantly more pronounced decrease in brain lead concentration in animals administered LA plus thiol chelators, compared to the effects of chelating agents alone. This is an interesting and notable observation, which requires further exploration. The results thus provide evidence of an encouraging role of LA when given in combination with a thiol chelator in the therapeutic intervention of lead poisoning, particularly in reducing the oxidative stress and brain lead concentration.     

Nicotinamide protects HCN2 cells from the free radical generating toxin,tertiary butylhydroperoxide (t-BuOOH)

In previous studies with mice the oxygen radical generating neurotoxin tertiary butylhydroperoxide (t-BuOOH) was used to mimic the oxidative injury that has been implicated in neurodegenerative diseases. In addition, previous studies have shown that the poly (ADP-ribose) polymerase (PARP) inhibitor nicotinamide is able to prevent DNA fragmentation and apoptosis that is induced by t-BuOOH in mouse brain. However, the molecular mechanism(s) by which nicotinamide is able to protect human brain cells at the cellular level is not clear. Therefore in this study a cell culture model system with human cortical neuronal cells (HCN2 cells) has been employed where the molecular mechanism(s) of nicotinamide action, both in the presence and absence of t-BuOOH has been studied. Human cortical neurons (HCN2 cells) have been shown to differentiate to a neuron-like morphology. In this study, exposure of HCN2 cells to t-BuOOH resulted in altered morphology and disruption of neuronal differentiation leading to cell death. However, in neurons, which were treated with nicotinamide before being exposed to t-BuOOH, neuronal differentiation was preserved; morphological disruption was prevented and cell death was reduced significantly. Moreover, our studies indicate that nicotinamide is able to prevent the up-regulation of the pro-apoptotic proteins p53 and p21/WAF-1, and the down-regulation of the anti-apoptotic protein bcl-2 that is induced by t-BuOOH in HCN2 cells. Thus this study indicates that nicotinamide protects human brain cells from the toxic effects of free radical generating toxins by regulating the levels of various pro- and anti-apoptotic proteins.     

National vitamin a prophylaxis programme : Need for change in current age strategy

Child survival and Safe Motherhood Programme emphasises on giving vitamin A prophylaxis upto three years of age only, contrary to earlier practice of its administration upto six years of age, based on the assumption of reduction of serious manifestations of vitamin A deficiency three years of age onwards. A cross-sectional study enrolling 1094 children was done to investigate vitamin A deficiency in under six children in urban slums of Nagpur city in Central India in post CSSM scenario. Clinical as well as subclinical (detected by abnormal conjunctival impression cytology) assessment of vitamin A status was performed according to standard procedures, as per WHO recommendations. The overall prevalence of xerophthalmia was 8.7%. Only milder manifestations of xerophthalmia were observed. Significantly higher prevalence of xerophthalmia was observed in more than three years of age. Although nonsignificant, higher prevalence of subclinical vitamin A deficiency was observed in above three years of age group. In view of current age strategy for vitamin A supplementation (< or = 3 years) and observed higher prevalence of clinical and subclinical vitamin A deficiency above three years of age in this study (also endorsed by earlier studies) a call for review of current age strategy for vitamin A supplementation is warranted.     

Preserved pharmacological activity of hepatocytes-treated extracts of valerian and St. John's wort

The two herbal extracts valerian (Valeriana officinalis L.) and St. John's wort (Hypericum perforatum L.) were studied for their metabolic changes upon incubation with freshly prepared rat hepatocytes and subsequently analysed phytochemically as well as pharmacologically in vitro. Quantitative HPLC analysis of valerian extracts revealed considerable metabolic activities with regard to sesquiterpenes and iridoids. The amount of acetoxyvalerenic acid decreased 9-fold, while that of hydroxyvalerenic acid correspondingly increased 9-fold due to O-deacetylation. The valepotriates didrovaltrate, isovaltrate and valtrate decreased 2-, 18- and 16-fold, respectively. However, the binding affinities of the incubated extracts to the benzodiazepine and picrotoxin binding site of the GABA (A) receptor were quite similar to those of the non-incubated extracts. Neither valerenic acids nor valepotriates exhibited any significant effect on the two binding sites when tested as single compounds. Therefore, either other constituents represent the active ones or multiple compounds are necessary for the observed inhibitory and allosteric effects at the GABA (A) receptor. Extracts of St. John's wort were less potently metabolised than valerian. The amount of pseudohypericin and the main flavonoids (hyperoside, rutin, isoquercitrin, quercitrin, quercetin and I3,II8-biapigenin) slightly decreased during the 4-h incubation period. Both the antagonist effect at the corticotropin-releasing factor (CRF) type 1 receptor and the binding inhibition at the 5-HT transporter were attenuated during the metabolic treatment. The reduced antagonist effect correlates with the decreasing amount of pseudohypericin known to be a CRF (1) receptor antagonist. In conclusion, the incubation of plant extracts with freshly prepared rat hepatocytes represents a useful approach to study the pharmacological action of metabolised plant extracts. The consistent pharmacological activity of both valerian and St. John's wort is concordant with the known clinical efficacy of pharmacological activities.