Prevalence and risk factors of hepatitis B virus, hepatitis C virus, and human immunodeficiency virus infections among drug addicts in Bangladesh

This cross-sectional study investigated the prevalence and risk factors of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections among 266 drug users attending a drug-addiction treatment centre in Dhaka, Bangladesh, from November 1996 to April 1997. Of the 266 addicts, 129 were injectable drug users (IDUs), and 137 were non-injectable drug users (non-IDUs). The seroprevalences of hepatitis B virus surface antigen (HBsAg), anti-HBc, anti-HBs, and anti-HCV antibodies among the IDUs were 8 (6.2%), 41 (31.8%), 15 (11.6%), and 32 (24.8%), and among the non-IDUs were 6 (4.4%), 33 (24.1%), 9 (6.6%), and 8 (5.8%) respectively. None of the drug users were positive for anti-HIV antibody. Although the prevalence of HBV infection did not significantly differ between the IDUs and the non-IDUs, the prevalence of HCV infection was significantly higher among the IDUs. Among the IDUs, the prevalence of both HBV and HCV infections was associated with sharing of needles and longer duration of injectable drugs used. The seroprevalence of HBV infection in both IDUs and non-IDUs was significantly higher among those who had a history of extramarital and premarital sex. The prevalence of HCV infection was not associated with sexual promiscuity. There was no association between the seroprevalence of HBV and HCV infections and age. Active preventive programmes focusing on educational campaigns among the youths against substance abuse should be undertaken.     

Tau phosphatase activity as a therapeutic target for AD

In the normal brain, tau promotes the assembly of tubulin into microtubules and maintains the structure of microtubules, which are required for axonal transport. Tau in AD brain is abnormally hyperphosphorylated ("AD P-tau") and does not promote the in vitro assembly of microtubules, bind to microtubules or stabilize their structure. Employing phosphorylation-dependent antibodies to tau, site-specific dephosphorylation of AD P-tau has been investigated. The phos-phoseryl/phosphothreonyl protein phosphatases (PSPs) PP-1, PP-2A and PP-2B rapidly dephosphorylated AD P-tau in vitro. The dephosphorylation of neurofibrillary tangles of paired helical filaments by the two major tau phosphatases, PP-2A and PP-2B, has been demonstrated to produce marked biochemical, biological and structural alterations. Thus, by increasing the activity of one more of these tau phosphatases, it might be possible to prevent and inhibit neuronal degeneration and consequently both the sporadic and the familial forms of AD.     

Ambient Temperature and Mortality From Unintentional Cocaine Overdose

Context.— Hot weather taxes cardiovascular function and is associated with increased deaths from heart disease. Cocaine can cause hypertension, tachycardia, coronary vasospasm, arrhythmias, and increased core temperature. Objective.— To determine the association between mortality from cocaine overdose and hot weather. Setting.— New York, NY. Design.— Retrospective review of medical examiner cases from 1990 through 1995. Subjects.— All fatal unintentional cocaine overdoses from 1990 through 1992 (n=1382) and all hyperthermia deaths of cocaine users (n=10) were used to identify a maximum daily temperature threshold above which mortality from cocaine intoxication increased. The study population consisted of all fatal unintentional cocaine overdoses from 1993 through 1995 (n=2008) and 4 contemporaneous comparison groups that included fatal unintentional opiate overdoses (n=793), all other fatal unintentional overdoses (n=85), and a subset of homicides (n=4638) and fatalities from motor vehicle crashes (n=815). Main Outcome Measures.— The number of overdose deaths and the proportion of homicides and traffic fatalities with a positive cocaine toxicology test result on days with a maximum temperature above or below the temperature threshold. Results.— A threshold temperature of 31.1°C (88°F) was identified, above which the mean daily number of fatal cocaine overdoses increased steadily. On days with a maximum daily temperature of 31.1°C (88°F) or higher ("hot days"), the mean daily number of cocaine overdose deaths was 2.34 (SD=1.68), which was 33% higher than the mean on days with a maximum temperature of less than 31.1°C (88°F) (mean=1.76 [SD=1.37] (P<.001). In contrast, the mean number of opiate overdose deaths per day was 0.81 (SD=0.94) on hot days and 0.71 (SD=0.86) on other days (P=.28). For other drug overdose deaths, the mean number of deaths per day was 0.08 (SD=0.28) on hot days and 0.08 (SD=0.28) on other days (P=.69). Among homicides, the proportion with a positive cocaine toxicology test result was 18.9% on hot days and 19.5% on other days (P=.69), and among traffic fatalities, the proportions with positive cocaine toxicology test results were 9.5% on hot days and 10.3% on other days (P=.91). Conclusions.— High ambient temperature is associated with a significant increase in mortality from cocaine overdose. Based on our comparison groups, the increase is not explained by changes in cocaine use among the general population. Although cocaine use is dangerous on all days, it appears to be even more dangerous on hot days.      

Hypolipidemic and antioxidant properties of tocotrienol rich fraction isolated from rice bran oil in experimentally induced hyperlipidemic rats.

We investigated a dose-dependent hypolipidemic and antioxidant effect of tocotrienol rich fraction (TRF) isolated from rice bran oil on experimentally induced hyperlipidemic rats. Feeding of atherogenic diet (5% hydrogenated fat, 0.5% cholic acid and 1% cholesterol) for three weeks resulted in a significant increase in plasma triglyceride (3.3-fold) and total cholesterol (2.4-fold) levels. There was a 5-fold increase in the level of LDL cholesterol with only a small increase in HDL cholesterol. On the other hand, HMG-CoA reductase activity was significantly reduced in these animals. The formation of TBARS, thiobarbituric acid reactive substances, (86%) and conjugated dienes (78%) were also significantly higher in these rats compared to normals. After the induction of hyperlipidemia for three weeks, rats were supplemented with different doses of TRF for one week. TRF supplementation decreased the lipid parameters in a dose-dependent manner with an optimum effect at a dose of 8 mg TRF/kg/day. HMG-CoA reductase activity, which was increased after the withdrawal of atherogenic diet, remained significantly decreased during the TRF treatment. Feeding of TRF also decreased TBARS and conjugated dienes significantly. These results suggest that TRF supplementation has significant health benefits through the modulation of physiological functions that include various atherogenic lipid profiles and antioxidants in hypercholesterolemia.     

Long-term alteration in bodyweight and food restriction does not affect the gene expression of either preproorexin or prodynorphin in the sheep

Various hypothalamic neuropeptides are involved in central regulation of food intake and expression of genes encoding these peptides changes with alterations in the bodyweight/metabolic status/nutritional status. Orexin(s) and dynorphin have been implicated in the regulation of appetite and neuroendocrine systems, but the function of these peptides is not well understood. We have employed in situ hybridization to examine the effects of long-term alterations in the bodyweight on expression of mRNA for preproorexin and prodynorphin in the putative feeding centers of the ovine hypothalamus. Expression of preproorexin was localized to the dorsomedial hypothalamic nucleus, perifornical area and lateral hypothalamic area. Cells expressing prodynorphin were localized to the periventricular, supraoptic, paraventricular, ventromedial hypothalamic nuclei and the thalamus. Small numbers of single scattered cells were seen in other brain areas. A few scattered prodynorphin-expressing cells were found in the lateral hypothalamic area but, in contrast to observations in the rat, there was no colocalization with preproorexin. Long-term alterations in the bodyweight did not influence the level of expression of preproorexin or prodynorphin. These findings suggest that orexin and dynorphin may not play a direct role in appetite regulation in sheep, although regulation at the level of the receptors for these peptides remains a possibility.     

Linkage of scapuloperoneal spinal muscular atrophy to chromosome 12q24.1-q24.31

Scapuloperoneal (SP) syndromes are heterogeneous neuromuscular disorders which are characterized by weakness in the distribution of shoulder girdle and peroneal muscles. SP syndromes can resemble facioscapulohumeral muscular dystrophy (FSH) due to scapular weakness or Charcot-Marie-Tooth disease (CMT) due to atrophy of peroneal muscles. Both neurogenic and myopathic SP syndromes have been described. Locus for the myopathic form of SP syndrome (scapuloperoneal muscular dystrophy, SPMD) has recently been assigned to chromosome 12q. We previously described a large New England kindred exhibiting an autosomal dominant neurogenic SP syndrome (scapuloperoneal spinal muscular atrophy, SPSMA). Disease expression was more severe and progressive in successive generations, which suggested genetic anticipation. We performed genetic linkage analysis of this family with microsatellite markers and excluded the loci for FSH, CMT, SPMD and SMA (spinal muscular atrophy) in our family. Linkage in our SPSMA family (lod score > 3) was established to seven microsatellite markers that map to chromosome 12q24.1-q24.31. The highest lod score with two-point linkage analysis was 6.67 (theta = 0.00) with marker D12S353. Multipoint analysis gave maximum lod scores of 7.38 between D12S354 and D12S79, and also 7.38 between D12S369 and NOS1 (neuronal nitric oxide synthase). The gene for SPSMA lies within the 19 cM interval between D12S338 and D12S366. This report establishes a locus for the neurogenic form of SP syndrome approximately 20 cM telomeric to the one described for the myopathic form of SP syndrome.      

Renal handling of phenol red. I. A comparative study on the accumulation of phenol red and p-aminohippurate in rabbit kidney tubules in vitro

1. The characteristics of renal accumulation of phenol red and p-aminohippurate (PAH) by slices of rabbit kidney cortex suspended in an electrolyte medium have been compared.2. It has been found that at low medium concentrations the accumulation of phenol red is about 4-5 times as high as that of PAH. Furthermore, phenol red is accumulated by the renal tissue under anaerobic conditions, in contrast to PAH.3. Experiments involving incubation of slices at low temperatures and addition of various metabolic inhibitors to the medium, indicate that the anaerobic accumulation of phenol red is due to binding to cellular constituents. This conclusion is corroborated by studies on renal homogenates from which it appears that phenol red is bound predominantly to the microsomal and mitochondrial fraction.4. The aerobic accumulation of phenol red is less susceptible to inhibition by probenecid, 2,4-dinitrophenol (DNP), and octanoate than is that of PAH. Besides, probenecid, DNP, and octanoate inhibit phenol red binding to the microsomal fraction, whereas mitochondrial binding of phenol red is unaffected by the presence of these substances.5. Fumarate and succinate affect the aerobic accumulation of phenol red and PAH to the same degree. Furthermore, fumarate, succinate, and PAH do not alter anaerobic accumulation of phenol red.6. It is concluded that probenecid, DNP, and octanoate cause more inhibition of organic anion transport than fumarate, succinate, and PAH because of lipophilic interaction with the membrane. The pronounced resistance of phenol red accumulation to inhibition by lipophilic inhibitors is probably due to the ability of the indicator dye to displace these substances from binding sites on the transporting membranes.     

Noninvasive assessment of cardiac risk in insulin-dependent diabetic patients being evaluated for pancreatic transplantation using thallium-201 myocardial perfusion scintigraphy

We examined the value of thallium-201 myocardial perfusion scintigraphy in noninvasive assessment of cardiac risk in 36 insulin-dependent (type 1) diabetic patients being evaluated for pancreas or combined pancreas/kidney transplantation. An extensive cardiovascular evaluation including electrocardiogram was performed in all patients, and most patients were also evaluated by two-dimensional and Doppler echocardiography. Exercise thallium studies were performed in 31 patients. Five patients were unable to exercise and underwent dipyridamole-thallium study. The thallium images were abnormal in 12 patients, 10 of whom underwent coronary arteriography. Significant coronary artery disease was found in 7 of these patients. Nineteen patients underwent pancreatic (3 patients) or pancreato-renal (16) transplantation without any occurrence of cardiac death or nonfatal myocardial infarction peri-operatively or on follow-up ranging from 7 months to 21 months. In contrast, 3 cardiac events occurred in 12 patients not approved for transplantation, each of whom had an abnormal thallium study exhibiting significant ischemia. Resting left ventricular global and regional function was not helpful in determining perioperative risk. Thus, thallium-201 myocardial perfusion scintigraphy may be useful in identifying diabetic patients at low risk for pancreas transplantation and may obviate the need for routine coronary angiography in these patients.