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Biomedical subjects

K Zaman

Publications and source records attributed to K Zaman.

At least 37 records · Page 2Linked to original sources

Reduced food consumption increases water intake and modulates renal aquaporin-1 and -2 expression in autoimmune prone mice.

Aquaporin-1(AQP1) and AQP2 are members of the aquaporin family of cell membrane water channel transport proteins and have been implicated in the regulation of renal water excretion. We have previously shown that calorie restriction (CR) relative to ad libitum (AL) feeding extends lifespan and delays the onset of autoimmune kidney disease in lupus-prone (NZBxNZW)F1 (B/W) mice. To determine if AQP1 and/or AQP2 expression is influenced by CR, mice were fed an AL or CR (40% less food) diet until 4 (young) or 9 (old) months of age when mice were sacrificed. Kidneys were removed and the expression of AQP1 and AQP2 was determined at the protein and mRNA levels using western blotting and RT-PCR respectively. While age did not significantly increase AQP1 expression in the AL groups, CR did increase both the protein (1.4-fold) and mRNA (2.4-fold) levels. In old mice, AQP1 expression was higher (1.8-fold) in CR compared to the AL group while CR had no effect in young mice. In contrast, AQP2 showed an age related decrease (55%) in the AL groups and an increase in the protein (8.4-fold) and mRNA (1.7-fold) levels in the CR groups. Relative to AL, CR decreased AQP2 expression at the protein (90%) and mRNA (50%) levels in the young mice while an increase at the protein (2.9-fold) and mRNA (1.9-fold) levels was evident in the old mice. Interestingly, a significant increase in water intake per gram body weight was found in both young and old CR fed mice when compared to their AL counterparts which may contribute to the prevention of autoimmune disease with age and differences in longevity. These data show, for the first time, significant age and diet influences in renal AQP1 and AQP2 expression at both protein and mRNA levels in lupus-prone mice.

Age Factors↗

Calorie restriction decreases proinflammatory cytokines and polymeric Ig receptor expression in the submandibular glands of autoimmune prone (NZB x NZW)F1 mice.

Calorie restriction or fish oil (enriched in n-3 fatty acids) supplementation ameliorates glomerulonephritis and Sjögren's syndrome lesions in (NZB x NZW)F1(B/W) mice. Enhanced proinflammatory cytokine expression and deposition of immune complexes are the important pathological events in the development of Sjögren's syndrome. In the present study, we have examined the effect of calorie restriction and fish oil supplementation on the expression of key inflammatory cytokines [gamma interferon (INF-gamma), interleukin-10 (IL-10), and IL-12] and polymeric immunoglobulin (Ig) receptor (pIgR) (receptor for IgA and IgM) and the secretion of Ig in the submandibular glands (SMG) of B/W mice. Weanling B/W mice were fed either ad libitum (AL) or calorie restricted (CR) (40% less calories than AL) diet supplemented with 5% corn oil (CO) or 5% fish oil (FO) until 4 or 9 months of age. The SMGs were removed and a portion of the tissue used for semiquantitive determinations of IFN-gamma, IL-10, IL-12 (p40), and pIgR mRNA. The remaining SMG tissue was fragmented and cultured for 7 days and the culture supernatants assayed for IgA, IgM, and IgG2a levels by enzyme-linked immunosorbent assay. Results revealed a significant increase in the expression of IFN-gamma, IL-10, and IL-12 mRNA with age in AL fed mice, whereas CR fed mice maintained their levels to near those seen in young animals regardless of the dietary fat. PIgR mRNA expression also remained unaltered in CR animals irrespective of age and dietary fat, while it was found significantly increased in AL fed mice. CR significantly inhibited the elevated levels of IgA and IgG2a seen in aged mice. Interestingly, CR also influenced the Ig level in young animals. In summary, these results indicate that amelioration of autoimmune disease by CR in B/W mice is possibly mediated by the lowered mRNA expression of IFN-gamma, IL-10, IL-12, and pIgR and the reduced Ig secretion.

Animals↗

Dietary (n-6) and (n-3) fatty acids and energy restriction modulate mesenteric lymph node lymphocyte function in autoimmune-prone (NZB x NZW)F1 mice.

We previously showed that dietary fish oil (FO) and energy restriction (R) have beneficial anti-inflammatory properties in the peripheral blood and spleens of (NZB x NZW)F1 (B/W) lupus-prone mice. Furthermore, unsaturated fatty acids also were shown in the past to influence mesenteric lymph node (MLN) lymphocyte function in healthy young rats. The MLN play a pivotal role in mediating food allergy. To date, the effect of R on intestinal immunity is not well understood; therefore we determined the effect of diet on MLN lymphocyte function. Mice were given either free access to a 5 g/100 g corn oil (CO) or fish oil (FO) diet or the same corn oil (CR) or fish oil (FR) diets restricted to 60% of the intake of the control group. At the age of 4 (young) and 8 (old) mo, MLN lymphocytes were isolated and B- (CD19(+)) and T-lymphocyte subsets (CD4(+) and CD8(+)) were determined by flow cytometry. Additional MLN lymphocytes were placed in culture with or without concanavalin A and culture supernatants collected after 72 h for cytokine and immunoglobulin (Ig) quantitation by ELISA. Aging significantly (P < 0.05) decreased both CD4(+) and CD8(+) T-lymphocytes. Spontaneous and activation-induced interleukin-4 (IL-4), IL-10, and interferon-gamma secretion were greater while IL-2 was lower in CO-fed old mice compared to CO-fed young mice. In contrast, CR or FO alone partially blunted the age-dependent alterations in T-lymphocyte ratios including cytokine and Ig secretion, whereas the FR diet significantly (P < 0.005) normalized the accelerated aging effects on these immune variables. We show for the first time that FR is a far more potent anti-inflammatory therapy than either CR or FO alone in modulating MLN lymphocyte function.

Aging↗

Perception and practice of rest during pregnancy among mothers and family decision-makers.

The incidence of low birthweight (LBW) in Bangladesh is one of the highest in the world. Inadequate rest of the mothers during pregnancy is a contributing factor to LBW. To assess the perception and practice of rest during pregnancy, 136 mothers and family members who make important decisions on family matter (FDM) were studied in rural Bangladesh. Eighty per cent of mothers perceived the importance of rest during pregnancy, whereas only 29 per cent practised rest (p < 0.003). Of the mothers who lacked perception, none practised. Eighty-five per cent of FDM perceived rest as important, yet only 27 per cent practised rest. Mothers' education and socioeconomic status were significantly associated with perception (p < 0.028,p < 0.001) and practice (p < 0.008,p < 0.006) of rest. The mother's education was also significantly (p < 0.000) associated with the socioeconomic status of the family. Our study suggests that the inability to take rest was due to workload at home, illiteracy, low socioeconomic status and failure of family members to share the workload.

Adolescent↗

Protection from oxidative stress-induced apoptosis in cortical neuronal cultures by iron chelators is associated with enhanced DNA binding of hypoxia-inducible factor-1 and ATF-1/CREB and increased expression of glycolytic enzymes, p21(waf1/cip1), and erythropoietin.

Iron chelators are pluripotent neuronal antiapoptotic agents that have been shown to enhance metabolic recovery in cerebral ischemia models. The precise mechanism(s) by which these agents exert their effects remains unclear. Recent studies have demonstrated that iron chelators activate a hypoxia signal transduction pathway in non-neuronal cells that culminates in the stabilization of the transcriptional activator hypoxia-inducible factor-1 (HIF-1) and increased expression of gene products that mediate hypoxic adaptation. We examined the hypothesis that iron chelators prevent oxidative stress-induced death in cortical neuronal cultures by inducing expression of HIF-1 and its target genes. We report that the structurally distinct iron chelators deferoxamine mesylate and mimosine prevent apoptosis induced by glutathione depletion and oxidative stress in embryonic cortical neuronal cultures. The protective effects of iron chelators are correlated with their ability to enhance DNA binding of HIF-1 and activating transcription factor 1(ATF-1)/cAMP response element-binding protein (CREB) to the hypoxia response element in cortical cultures and the H19-7 hippocampal neuronal cell line. We show that mRNA, protein, and/or activity levels for genes whose expression is known to be regulated by HIF-1, including glycolytic enzymes, p21(waf1/cip1), and erythropoietin, are increased in cortical neuronal cultures in response to iron chelator treatment. Finally, we demonstrate that cobalt chloride, which also activates HIF-1 and ATF-1/CREB in cortical cultures, also prevents oxidative stress-induced death in these cells. Altogether, these results suggest that iron chelators exert their neuroprotective effects, in part, by activating a signal transduction pathway leading to increased expression of genes known to compensate for hypoxic or oxidative stress.

Activating Transcription Factor 1↗

Oxidative stress as a mechanism of chronic cadmium-induced hepatotoxicity and renal toxicity and protection by antioxidants.

The role of oxidative stress in chronic cadmium (Cd) toxicity and its prevention by cotreatment with antioxidants was investigated. Adult female Sprague-Dawley rats were injected sc with 5 micromol CdCl2/kg/day, 5 times a week, for up to 22 weeks. Serum alanine amino transferase and lactate dehydrogenase activities were elevated after 9 weeks of Cd administration, indicating hepatic damage. Renal toxicity, indicated by elevation in urinary lactate dehydrogenase activity and protein, was also observed around this time. Chronic Cd administration resulted in a gradual rise in hepatic as well as renal cortex glutathione levels. In spite of this, lipid peroxidation increased in both tissues, particularly during the second half of the Cd exposure period. Depletion of glutathione following buthionine sulfoximine administration at the end of Week 5, or inhibition of catalase by aminotriazole at the end of Week 7, resulted in the development of acute nephrotoxicity within 6 h. Coadministration of antioxidants, N-acetylcysteine (50-100 mg/kg, sc), or vitamin E (100-150 mg/kg, sc) with Cd, starting from the early phases of Cd exposure, controlled Cd-induced lipid peroxidation and protected the animals against hepatic as well as renal toxicity. A Japanese hepatoprotective drug, Stronger Neo-Minophagen C, containing glycyrrhizin, glycine, and cysteine, was also effective in reducing the chronic Cd nephrotoxicity. In conclusion, oxidative stress appears to play a major role in chronic Cd-induced hepatic and renal toxicity since inhibition of components of the antioxidant defense system accelerated and administration of antioxidants protected against Cd toxicity.

Acetylcysteine↗

Treatment of chronic cadmium nephrotoxicity by N-acetyl cysteine.

Chronic cadmium (Cd)-induced nephrotoxicity is believed to be irreversible at advanced stages and no treatment is currently available. This study examined the beneficial effect of N-acetyl cysteine (NAC) on Cd-induced nephrotoxicity. Female Sprague-Dawley rats were injected s.c. with 5 micromol CdCl2/kg per day, five times/week for up to 26 weeks. Nephrotoxicity was detected after 10 weeks by elevation in urinary lactate dehydrogenase activity and protein. NAC co-administration from week 13 prevented the progression of nephrotoxicity. In these animals, with low-level nephrotoxicity, discontinuation of Cd exposure at the end of week 22 resulted in gradual recovery over the next several weeks, without the need for treatment with NAC. On the other hand, discontinuation of NAC co-treatment at the end of week 22 resulted in quick progression of nephrotoxicity, indicating that NAC protection was short-lived. Resumption of NAC treatment and cessation of Cd exposure after 26 weeks resulted in rapid recovery from advanced nephrotoxicity. It is concluded that protection from Cd-induced nephrotoxicity is possible by continued co-administration of NAC and that recovery from advanced nephrotoxicity can also be achieved with NAC, provided that Cd exposure is stopped.

Acetylcysteine↗

Molecular characterization of a new ribotype of Vibrio cholerae O139 Bengal associated with an outbreak of cholera in Bangladesh.

Vibrio cholerae O139 Bengal initially appeared in the southern coastal region of Bangladesh and spread northward, causing explosive epidemics during 1992 and 1993. The resurgence of V. cholerae O139 during 1995 after its transient displacement by a new clone of El Tor vibrios demonstrated rapid changes in the epidemiology of cholera in Bangladesh. A recent outbreak of cholera in two north-central districts of Bangladesh caused by V. cholerae O139 led us to analyze strains collected from the outbreak and compare them with V. cholerae O139 strains isolated from other regions of Bangladesh and neighboring India to investigate their origins. Analysis of restriction fragment length polymorphisms in genes for conserved rRNA (ribotype) revealed that the recently isolated V. cholerae O139 strains belonged to a new ribotype which was distinct from previously described ribotypes of toxigenic V. cholerae O139. All strains carried the genes for toxin-coregulated pili (tcpA and tcpI) and accessory colonization factor (acfB), the regulatory gene toxR, and multiple copies of the lysogenic phage genome encoding cholera toxin (CTXPhi) and belonged to a previously described ctxA genotype. Comparative analysis of the rfb gene cluster by PCR revealed the absence of a large region of the O1-specific rfb operon downstream of the rfaD gene and the presence of an O139-specific genomic region in all O139 strains. Southern hybridization analysis of the O139-specific genomic region also produced identical restriction patterns in strains belonging to the new ribotype and those of previously described ribotypes. These results suggested that the new ribotype of Bengal vibrios possibly originated from an existing strain of V. cholerae O139 by genetic changes in the rRNA operons. In contrast to previously isolated O139 strains which mostly had resistance to trimethoprim, sulfamethoxazole, and streptomycin encoded by a transposon (SXT element), 68.6% of the toxigenic strains analyzed in the present study, including all strains belonging to the new ribotype, were susceptible to these antibiotics. Molecular analysis of the SXT element revealed possible deletion of a 3.6-kb region of the SXT element in strains which were susceptible to the antibiotics. Thus, V. cholerae O139 strains in Bangladesh are also undergoing considerable reassortments in genetic elements encoding antimicrobial resistance.

Bangladesh↗

Purification of a multipotent antideath activity from bovine liver and its identification as arginase: nitric oxide-independent inhibition of neuronal apoptosis.

Catalase is an antioxidant enzyme that has been shown to inhibit apoptotic or necrotic neuronal death induced by hydrogen peroxide. We report the purification of a contaminating antiapoptotic activity from a commercial bovine liver catalase preparation by following its ability to inhibit apoptosis when applied extracellularly in multiple death paradigms. The antiapoptotic activity was identified by protein microsequencing as arginase, a urea cycle and nitric oxide synthase-regulating enzyme, and confirmed by demonstrating the presence of antiapoptotic activity in a >97% pure preparation of recombinant arginase. The pluripotency of recombinant arginase was demonstrated by its ability to inhibit apoptosis in multiple paradigms including rat cortical neurons induced to die by glutathione depletion and oxidative stress, by 100 nM staurosporine treatment, or by Sindbis virus infection. The protective effects of arginase in these apoptotic paradigms, in contrast to previous studies on excitotoxic neuronal necrosis, are independent of nitric oxide synthase inhibition. Rather, arginase-induced depletion of arginine leads to inhibition of protein synthesis, resulting in cell survival. Because inhibitors of nitric oxide synthesis and of protein synthesis have been shown to decrease necrotic and apoptotic death, respectively, in animal models of stroke and spinal cord injury, arginine-depleting enzymes, capable of simultaneously inhibiting protein synthesis and nitric oxide generation, may be propitious therapeutic agents for acute neurological diseases. Furthermore, our results suggest caution in attributing the cytoprotective effects of some catalase preparations to catalase.

Amino Acid Sequence↗

Acute respiratory infections in children: a community-based longitudinal study in rural Bangladesh.

A community-based logitudinal study conducted in Matlab, a rural area in Bangladesh, investigated acute respiratory infections (ARI) among children. A cohort of 696 children under 5 years of age was followed for 1 year yielding 183,865 child-days of observation. Trained field workers visited the study children every fourth day. Data on symptoms suggesting ARI, such as fever, cough, and nasal discharge, were collected for the preceding 3 days by recall. To determine the type and severity of ARI, the field workers conducted physical examinations (temperature, rate of respiration, and chest indrawing) of children reporting cough and/or fever. The overall incidence of ARI was 5.5 episodes per child-year observed; the prevalence was 35.4 per hundred days observed. Most of the episodes (96 per cent) were upper respiratory infections (URI). The incidence of acute lower respiratory infections (ALRI) was 0.23 per child per year. The incidence of URI was highest in 18-23-month-old children, followed by infants 6-11 months old. The highest incidence of ALRI was observed in 0-5-month-old infants followed by 12-17-month-old children. Among 559 children who were followed for 6 months or longer, about 9 per cent did not suffer any URI episode and about 16 per cent suffered one or more ALRI episodes. About 46 per cent of URI and 65 per cent of ALRI episodes lasted 15 days or more. The incidence rates of URI were higher during the monsoon and pre-winter periods, and that of ALRI at the end of the monsoon and during the pre-winter periods. Sociodemographic variables were not associated with the incidence of URI or ALRI. The study documents ARI to be a major cause of morbidity among rural Bangladeshi children.

Bangladesh↗

Malnutrition, cell-mediated immune deficiency and acute upper respiratory infections in rural Bangladeshi children.

A community-based longitudinal study conducted in rural Bangladesh investigated the association between nutritional status, cell-mediated immune status and acute upper respiratory infections (URI). A total of 696 children aged 0-59 months was followed prospectively for 1 y yielding 183,865 child-days' observation. Trained field workers visited each child every 4th d and collected morbidity data on symptoms suggesting URI (cough, fever, nasal discharge) for the preceding 3 d by recall. On the day of visit they examined each child reporting cough and/or fever to record the temperature, presence of nasal discharge, rate of respiration and presence of chest indrawing. Anthropometry for all children was conducted monthly. Cell-mediated immune competence was assessed by a multiple antigen skin test at baseline and thereafter every 3 months. The incidence of URI was 5.3 episodes per child-year observed. Approximately three-quarters of the study children were below -2 Z-score weight for age and height for age, and a quarter below -2 Z-score weight for height. During different test periods 9-21% of the study children did not respond to any of the test antigens. In a regression model children < -2 Z-score for weight for height had 16% [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.03-1.31, p = 0.01] higher risk of developing URI. Anergic children had 20% higher risk (OR 1.20, CI 1.05-1.38, p = 0.009) of URI than immunocompetent children. The study demonstrated that wasting and depressed cell-mediated immunity (CMI), but not stunting, were associated with the incidence of URI among rural Bangladeshi children.

Anthropometry↗

Molecular analysis of toxigenic Vibrio cholerae O139 Bengal strains isolated in Bangladesh between 1993 and 1996: evidence for emergence of a new clone of the Bengal vibrios.

Vibrio cholerae O139 Bengal emerged in 1992 and rapidly spread in an epidemic form, in which it replaced existing strains of V. cholerae O1 in Bangladesh during 1992 and 1993. The subsequent emergence of a new clone of V. cholerae O1 of the El Tor biotype that transiently displaced the O139 vibrios during 1994 to 1995 and the recent reemergence of V. cholerae O139 and its coexistence with the El Tor vibrios demonstrated temporal changes in the epidemiology of cholera in Bangladesh. We studied clonal diversity among V. cholerae O139 strains isolated from cholera patients and environmental surface water since their first appearance until their transient disappearance in 1994 as well as the O139 strains that reemerged during 1995 to 1996 and were isolated in the capital Dhaka and four rural districts of Bangladesh to investigate the origin of the reemerged strains. Analysis of restriction fragment length polymorphisms in genes for conserved rRNA and cholera toxin (CT) (ctxA) or in DNA sequences flanking these genes revealed four different ribotypes and four different ctx genotypes among the 93 strains of V. cholerae O139 studied. Ribotypes I and II and ctx genotypes A through C were shared by strains isolated from the epidemic outbreak during 1992 and 1993 in Bangladesh and India, ribotype III was represented by a single CT-negative O139 strain from Argentina, and 16 of 27 (59.2%) of the reemerged strains isolated during 1995 and 1996 belonged to a new ribotype of O139 vibrios designated ribotype IV. All 16 strains belonging to ribotype IV also belonged to a new ctx genotype (genotype 4). These results provide evidence for the emergence of a new clone of toxigenic V. cholerae O139 in Bangladesh. Further analysis of the rfb gene cluster by PCR revealed the absence of a large region of the O1-specific rfb operon and the presence of an O139-specific genomic region in all O139 strains. The PCR amplicon corresponding to the rfaD gene of a CT-negative O139 strain from Argentina was smaller in length than those of the toxigenic O139 strains but was identical to those of seven non-O1 and non-O139 strains. All O139 strains except the CT-negative strain carried structural and regulatory genes for CT and toxin-coregulated pili (ctxA, tcpA, tcpI, and toxR). These results suggest that the O139 Bengal strains possibly emerged from an El Tor strain but that the CT-negative non-Bengal O139 strain might have emerged from a non-O1, non-O139 strain. Thus, strains belonging to the O139 serogroup may have emerged from similar serotype-specific genetic changes in more than one progenitor strain of V. cholerae.

Bacterial Outer Membrane Proteins↗

Acute lower respiratory infections in rural Bangladeshi children: patterns of treatment and identification of barriers.

A study conducted in rural Bangladesh examined the patterns of health seeking behavior, mothers' recognition of symptoms, the perceived causes and barriers to timely treatment of acute lower respiratory infections (ALRI). A total of 194 children under 5 years of age suffering from ALRI in an intensive maternal child health and family planning area was prospectively followed. About 62% of the mothers sought allopathic treatment for their children within 24 hours of case detection. No treatment of any kind was sought in 45 (23.2%) cases. Most of the mothers could recognize the different symptoms of ALRI. Cold was reported as the most common cause of ALRI. No significant difference was observed in the reported symptoms or perceived cause of the disease between those who sought no treatment and those who sought allopathic, homeopathic, spiritual or combined treatments. Failure to recognize severity followed by work loss were the most common reasons identified for not seeking any medical care. Whether or not a mother sought allopathic treatment was not associated with the child's age, sex, mother's age, mother's education, duration of illness, birth order, housing type or distance from the health center. The study indicates the potential value of giving parents clear guidelines on recognition of severity of symptoms of ALRI and motivating them to seek treatment quickly when these symptoms present. Health service providers should be aware of the heavy work loads which rural women have and the severe time constraints which deter them from seeking timely treatment from the appropriate sources.

Bangladesh↗

Vibrio cholerae O139: how great is the threat of a pandemic?

The emergence of the new strain Vibrio cholerae O139 and its rapid spread in Bangladesh and India together with its detection in several other countries, have raised the question whether this constitutes the beginning of the eighth pandemic of cholera, and if so, how large a threat it poses. In an attempt to answer this question, epidemic spread patterns of Vibrio cholerae O139 strain in Bangladesh were studied. Initially the epidemic moved quickly and affected the entire coastal and estuarine tidal plains of southern Bangladesh. In the flood plains of the northern regions it affected mostly the north-eastern and north-central areas, at a slower pace than in the southern areas. In the beginning the new strain totally displaced both biotypes (classic and El Tor) of Vibrio cholerae O1. Nearly 2 years after its initial detection, striking differences in the distribution of V. cholerae O139 and O1 were observed. In most northern areas, the new strain was replaced by V. cholerae O1, whereas in the southern coastal regions, the O139 strain continues to dominate epidemics. The study suggests that the O139 strain may become endemic in the coastal ecosystem. The threat of a pandemic, therefore, may not be as large as it first seemed.

Bangladesh↗

Association between nutritional status, cell-mediated immune status and acute lower respiratory infections in Bangladeshi children.

OBJECTIVE: To investigate the association between nutritional status, cell-mediated immune status and the incidence of acute lower respiratory infections (ALRI). DESIGN: Community-based longitudinal study. SETTING: Three villages in rural Bangladesh at Matlab. SUBJECT: 696 children aged 0-59 months were followed up for a year. METHODS: Trained field workers visited all children every fourth day and collected morbidity data for the preceding three days by recall. To determine the type and severity of respiratory infections, the field workers physically examined each child reporting a cough. Anthropometric status was determined monthly and cell-mediated immune status by skin tests was assessed at the beginning of the study and thereafter every 3 months. RESULTS: The incidence of ALRI was 23 episodes per 100 child-years. A total of 73-78% of the children were below -2 z score weight for age, 15-30% were below - 2 z score weight for height, and 68-76% were below -2 z score height for age. In logistic regression models, malnutrition as assessed by weight-for-height status [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.45-0.96, P = 0.03] or weight-for-age status (OR 0.64, 95% CI 0.45-0.92, P = 0.02) was significant predictor of ALRI. Anergic children had a higher risk of ALRI which approached to be statistically significant (OR 1.81, 95% CI 0.92-3.55, P = 0.08). CONCLUSIONS: Improvement of nutritional and cell-mediated immune status in rural Bangladeshi children should reduce the incidence of ALRI.

Acute Disease↗

Why treatment centres failed to prevent cholera deaths among Rwandan refugees in Goma, Zaire.

In July, 1994, in one of the worst cholera outbreaks in recent times, an estimated 12,000 Rwandan refugees died in Goma in eastern Zaire. The Vibrio cholerae strains were resistant to tetracycline and doxycycline, the commonly used drugs for cholera treatment. Despite the efforts of international organisations, which provided medical relief by establishing treatment centres in Goma, mortality from the disease was much higher than expected. In the area of Muganga camp, which had the largest concentration of refugees and where most of the medical aid organisations were active, the highest reported case-fatality ratio for a single day was 48%. The slow rate of rehydration, inadequate use of oral rehydration therapy, use of inappropriate intravenous fluids, and inadequate experience of health workers in management of severe cholera are thought to be some of the factors associated with the failure to prevent so many deaths during the epidemic. In one of the temporary treatment centres with the worst case-fatality record, our team showed that improvement of these factors could increase the odds of survival of cholera patients even in a disaster setting.

Ambulatory Care Facilities↗

An insect model for assessing oxidative stress related to arsenic toxicity.

The potential usefulness of an insect model to evaluate oxidative stress induced by environmental pollutants was examined with trivalent arsenic (As3+, NaAsO2) and pentavalent arsenic (As5+, Na2HAsO4) in adult female house flies, Musca domestica, and fourth-instar cabbage loopers, Trichoplusia ni. M. domestica was highly susceptible to both forms of arsenic following 48 h exposure in the drinking water with LC50s of 0.008 and 0.011% w/v for As3+ and As5+, respectively. T. ni larvae were susceptible to dietary As3+ with an LC50 of 0.032% w/w but seem to tolerate As5+ well with an LC50 of 0.794% concentration after 48 h exposure. The minimally acute LC5 dose of both As3+ and As5+ varied considerably but averaged 0.005% for both insects. The potential of both valencies of arsenic for inducing oxidative stress in the insects exposed ad libitum to approximately LC5 levels was assessed. The parameters examined were the alterations of the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST), the peroxidase activity of glutathione transferase (GSTPX), and glutathione reductase (GR), and increases in lipid peroxidation and protein oxidation. SOD (1.3-fold), GST (1.6-fold), and GR (1.5-fold) were induced by As3+ in M. domestica but CAT and GSTPX were not affected. As5+ had no effect on M. domestica. In T. ni, the antioxidant enzyme activities were not affected by As3+ except for SOD which was suppressed by 29.4% and GST which was induced by 1.4-fold. As5+ had no effect except the suppression of SOD by 41.2%. Lipid peroxidation and protein oxidation, which represent stronger indices of oxidative stress, were elevated in both insects by up to 2.9-fold. However, based on the antioxidant enzyme response to the arsenic anions, the mode of action of arsenic induced oxidative stress may differ between the two insects. Until this aspect is further clarified, evidence at this time favors the prospect of As3+ as a pro-oxidant, especially for M. domestica.

Animals↗

Dichlone-induced oxidative stress in a model insect species, Spodoptera eridania.

Southern armyworm, Spodoptera eridania, larvae were provided ad libitum 0.002-0.25% w/w dichlone, 2,3-dichloro-1,4-naphthoquinone (CNQ). Larval mortality occurred in a time-and-dose dependent manner, with an LC17 of 0.01% and an LC50 of 0.26% CNQ at day-5. Extracts of larvae fed control, 0.01, and 0.25% CNQ diets for 5 days were assayed for antioxidant enzymes. While 0.01% CNQ had a mild effect, 0.25% CNQ profoundly increased levels of all antioxidant enzymes that were examined. The increases as compared to control were: 5.3-, 1.9-, 3.2-, 2.6-, 2.8-, and 3.5-fold higher for superoxide dismutase, catalase, glutathione transferase and its peroxidase activity, glutathione reductase and DT-diaphorase, respectively. At 0.01% CNQ, the thiobarbituric acid reactive substances (TBARS) were similar to the control group. However, despite the induction from 0.25% CNQ of all enzymes examined, the lipid peroxidation was not attenuated; the TBARS were 29.7% over the control value. High mortalities and CNQ-induced pathologies reflected in retarded growth, wasting syndrome, and diuresis clearly indicated that the insect sustained severe oxidant-induced injuries before appropriate defenses were fully mobilized. Thus, this quinone causes an oxidative stress in a model insect species analogous to that observed in mammalian species.

Animals↗