Longitudinal study of cyclosporine and lipids in patients undergoing bone marrow transplantation

The metabolic effects of intravenous cyclosporine on lipids and lipoproteins were studied in 29 allogeneic bone marrow recipients compared with 13 autologous bone marrow patients not requiring cyclosporine therapy. Patients were monitored continuously from 5 days prior to 27 days following transplantation; cyclosporine treatment was initiated 4 days before transplantation. Fasting lipid and lipoprotein levels were measured in serial blood samples throughout the study period. Nutritional supplementation, conditioning regimens and concomitant medications were not significantly different between groups. Furthermore, no significant differences in age, weight, lipid, or lipoprotein levels were found at baseline between the patient groups. Cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels remained unchanged in autologous patients. As compared with baseline values, plasma total cholesterol increased by an average of 26 percent in allogeneic transplantation patients receiving cyclosporine. Similarly, the ratio of low-density lipoprotein to high-density lipoprotein cholesterol was fourfold greater in those patients treated with cyclosporine compared to the autologous group. We conclude that cyclosporine appears to elevate cholesterol levels. Neither acute graft vs host disease nor changes in hepatic function could explain the differences in plasma cholesterol levels between groups.     

Long-term male-specific chronic pain via telomere- and p53‑mediated spinal cord cellular senescence

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.     

Hepatitis C infection in children and adolescents with end-stage renal disease

The prevalence of hepatitis C virus (HCV) infection and the risk factors associated with its transmission are described in a contemporary cohort of 55 children and adolescents with end-stage renal disease (ESRD). Thirty-seven patients were on dialysis or had been transplanted (ESRD) and 18 had chronic renal failure (CRF) but had not yet received dialysis. Seven (19%) tested positive for HCV by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), or both. None of the children with CRF were infected. HCV infection was associated with length of time on dialysis, but not with age, gender, race, or units of blood transfused. These data corroborate earlier reports and confirm that children with ESRD continue to have a high prevalence of HCV. It is also shown for the first time that elevated transaminases should not be employed to predict HCV infection in this cohort, as all affected children had normal serum levels. Because of unique characteristics in this cohort, both ELISA and PCR are required to maximize HCV diagnostic sensitivity. Although HCV remains an important consideration in pediatric ESRD, the present study shows that recent advances in clinical practice have eliminated one of the major ways in which it was previously being transmitted. Received: 30 July 2001 / Revised: 2 January 2002 / Accepted: 4 January 2002     

Protease inhibitors modulate apoptosis in mesangial cells derived from a mouse model of HIVAN

BACKGROUND: Oxidative stress as well as opiate addiction has been shown to play a role in the development of complications associated with human immunodeficiency virus (HIV) infection. METHODS: We studied the occurrence of apoptosis in mesangial cells derived from control (NTrMC) mice and mice transgenic for HIV-1 genes (HTrMC) under basal and morphine-stimulated states (MSS). We evaluated the effect of free radical scavengers and antioxidants on HTrMC apoptosis and production of superoxide under basal and MSS. In addition, we examined the effect of protease inhibitors (PI) on apoptosis of NTrMCs/HTrMCs as well as morphine-induced superoxide dismutase (SOD) and nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase activation. RESULTS: HTrMCs showed greater apoptosis when compared with NTrMCs. Morphine triggered (P < 0.001) apoptosis of both NTrMCs and HTrMCs. Both antioxidants and free radical scavengers inhibited apoptosis of NTrMCs and HTrMCs under both basal and MSS. Morphine stimulated the production of superoxide by NTrMCs as well as by HTrMCs. Nevertheless, HTrMCs produced a greater (P < 0.001) amount of superoxide when compared with NTrMCs both under basal and MSS. PIs such as saquinavir and Indinavir inhibited HTrMC apoptosis in a dose-dependent manner. Saquinavir also protected HTrMCs against the proapoptotic effect of morphine. Moreover, saquinavir inhibited the production of superoxide by HTrMCs under both basal and MSS. Saquinavir also attenuated the morphine-induced expression of SOD and NADPH oxidase (Gp91phox) by HTrMCs. Interestingly, hemin exacerbated morphine-triggered HTrMC apoptosis. CONCLUSION: Oxidative stress seems to play a role in the accelerated rate of HTrMC apoptosis both under basal and MSS. Saquinavir may be inhibiting HTrMC apoptosis by mitigating oxidative stress.     

A single-center study of C1q nephropathy in children

C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.     

New challenges in family interventions for schizophrenia

This review first outlines the rationale and research base supporting the development of family interventions for schizophrenia. The over-riding principles guiding effective family interventions for schizophrenia are then presented, along with the key components (engagement, assessment, education, communication skills training and problem-solving) shared by most family programs in schizophrenia. Meta-analyses demonstrating the efficacy of family interventions in reducing relapse and rehospitalization in schizophrenia are then discussed, along with issues regarding minimal duration of effective treatment, differential benefits of single and multiple family modalities and mixed evidence for the maintenance of treatment effects after termination. The benefits of participation in family-organized, nonprofessional support and education programs are then described. Finally, three issues meriting further study are outlined.     

Comparative and evaluation of anti-leech (Limnatis Nilotica) effect of Olive (Olea Europaea L.) with Levamisol and Tiabendazole

ObjectiveUntil now, there is no registered drug for treatment of complications with leech in the world. According to the available scientific evidence, Olive is an effective anti-parasitic plant. Hence, in the present experiment we studied the inhibitory and killing effect of Olive methanolic extract on Limnatis nilotica.MethodsIn this study, 100 leeches (Limnatis nilotica) were collected from some wells in western area of Iran (south region in Ilam province) and evaluated the anti-leech effects of Olive methanolic extract (Olea europaea L.) in comparison with levamisole and tinidazole.ResultsThe results indicated no effect of tinidasole and distilled water on killing or mortality rate of the leeches but Olea europaea L. plant and levamisole have more effect on the L. nilotica. The mean death time of leech for levamisole and Olive determined 10±0.98 and 210±24.1 minutes, respectively.ConclusionsThe results showed that treatments of Olive methanolic extract and levamisole have the most effects on leeches and could be used as natural anti-L. nilotica. However it is necessary to achieve further studies for confirm of this subject.     

Pregnant Women in Women-Only and Mixed-Gender Substance Abuse Treatment Programs: A Comparison of Client Characteristics and Program Services

This study compared characteristics of pregnant women treated in women-only (WO) and mixed-gender (MG) substance abuse treatment programs and compared services provided by these two types of programs. Participants were 407 pregnant women who were admitted to 7 WO programs and 29 MG programs in 13 counties across California during 2000–2002. Pregnant women treated in WO programs demonstrated greater severity in drug use, legal problems, and psychiatric problems than those treated in the MG programs. They were also less likely to be employed and more likely to be homeless. Women-only programs were more likely to offer child care, children’s psychological services, and HIV testing. The greater problem severity of pregnant women treated in WO programs suggests that these specialized services are filling an important gap in addiction services, although further expansion is warranted in psychiatric, legal, and employment services.Noosha Niv, PhD, UCLA Integrated Substance Abuse Programs, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90025, USA.An erratum to this article can be found at     

Women-only and mixed-gender drug abuse treatment programs: service needs, utilization and outcomes

OBJECTIVES: This prospective longitudinal study examined service needs, utilization and outcomes for 189 women in women-only (WO) programs and 871 women in mixed-gender (MG) programs. METHODS: The Addiction Severity Index was administered at both intake and the 9-month follow-up interview to assess clients' problem severity and outcomes, and the Treatment Service Review was given at the 3-month interview to measure service utilization. Treatment completion and arrests were based on official records. RESULTS: Compared to women in MG programs, women in WO programs were more likely to be White, less educated, physically abused in the past 30 days and in residential treatment (as opposed to outpatient treatment). Women in WO programs also had greater problem severity in a number of domains including alcohol, drug, family, medical and psychiatric. They utilized more treatment services and had better drug and legal outcomes at follow-up compared to women in MG programs. Program type was not predictive of treatment retention/completion or outcomes in other domains (i.e., alcohol, employment, family, medical and psychiatric). CONCLUSIONS: The greater problem severity of women treated in WO programs and their better drug and legal outcomes suggest that these specialized services are filling an important gap in addiction services.