Anionic (i.e., acidic) phospholipids such as phosphotidylglycerol (PG) and cardiolipin (CL), participate in several cellular functions. Here we review intriguing in vitro and in vivo evidence that suggest emergent roles for acidic phospholipids in regulating DnaA protein-mediated initiation of Escherichia coli chromosomal replication. In vitro acidic phospholipids in a fluid bilayer promote the conversion of inactive ADP-DnaA to replicatively proficient ATP-DnaA, yet both PG and CL also can inhibit the DNA-binding activity of DnaA protein. We discuss how cellular acidic phospholipids may positively and negatively influence the initiation activity of DnaA protein to help assure chromosomal replication occurs once, but only once, per cell-cycle. Fluorescence microscopy has revealed that PG and CL exist in domains located at the cell poles and mid-cell, and several studies link membrane curvature with sub-cellular localization of various integral and peripheral membrane proteins. E. coli DnaA itself is found at the cell membrane and forms helical structures along the longitudinal axis of the cell. We propose that there is cross-talk between acidic phospholipids in the bacterial membrane and DnaA protein as a means to help control the spatial and temporal regulation of chromosomal replication in bacteria.
acidic phospholipids; DnaA protein; chromosomal replication; Escherichia coli
This work was carried out to study the hematologic profile of human immunodeficiency virus (HIV)-positive patients and its association with the clinicoimmunologic stage of the disease.
Materials and Methods:
A total of 187 patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme-linked immunosorbent assay (ELISA) method according to the National AIDS Control Organization (NACO) guidelines were included in this study. Patients in the study population were divided into two groups: (1) Group A (antiretroviral therapy (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment naïve patients (ART-N). The patients were tested for hemoglobin (Hb), total red blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC), platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm. The group or categorical data were tested for statistical significance using Chi-square test and Z-test. The difference was reported as significant if P < 0.05.
(1) Anemia (predominantly normocytic normochromic) was prevalent in 40.1%, with slightly higher prevalence in those not receiving ART. It occurred with high frequency in patients with immunological (42.05%) and clinical acquired immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an asymptomatic HIV infection with CD4 > 200/μl (28.57%). Patients on zidovudine (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2) Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.
Anemia; art; clinicoimmunologic stage; human immunodeficiency virus
We undertook a prospective study to assess the impact of HIV infection on BMD in a cohort of HIV-infected and uninfected women that included illicit drug users, and to measure the contribution of traditional risk factors as well as HIV-related factors to loss of BMD over time.
We analyzed BMD at baseline and after ≥18 months in 245 middle-aged HIV-infected and 219 uninfected women, and conducted linear regression analysis to determine factors associated with annual BMD change at the femoral neck, total hip and lumbar spine.
HIV-infected women had lower baseline BMD at the femoral neck and total hip compared with controls; unadjusted rates of BMD change did not differ by HIV status at any site. In multivariable analyses, we found that HIV seropositivity without protease inhibitor (PI) use was associated with BMD decline at the lumbar spine (−.009 gm/cm2 per year, p=.03.) Additional factors associated with BMD decline were: postmenopausal status, lower BMI, and methadone use at the lumbar spine; postmenopausal status and hepatitis C seropositivity at the femoral neck; and postmenopausal status, age, smoking, and lower BMI at the total hip (all p<.05). Among HIV-infected women, ≥3 years of PI use was associated with an increase in lumbar spine BMD (.013 gm/cm2 per year, p=.008.)
Bone loss among HIV–infected middle-aged women was modest, and possibly mitigated by PI use. Methadone use was associated with BMD decline, and should be considered when evaluating women for osteoporosis risk.
osteopenia; osteoporosis; bone mineral density; HIV; women
Solanum nigrum is used in various traditional medical systems for antiproliferative, antiinflammatory, antiseizure and hepatoprotective activities. We have evaluated organic solvent and aqueous extracts obtained from berries of Solanum nigrum for antiproliferative activity on leukemic cell lines, Jurkat and HL-60 (Human promyelocytic leukemia cells). The cell viability after the treatment with Solanum nigrum extract was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay. Results indicated increased cytotoxicity with increasing extract concentrations. Comparative analysis indicated that 50% inhibitory concentration value of methanol extract is the lowest on both cell lines.
Cytotoxicity; HL-60; Jurkat; MTT assay; Solanum nigrum
Vitamin D deficiency is of increasing concern in HIV-infected persons, because of its reported association with a number of negative health outcomes that are common in HIV. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a nationally representative cohort of middle-aged, ethnically diverse HIV-infected and uninfected women enrolled in the Women’s Interagency HIV study (WIHS).
Vitamin D testing was performed by Quest Diagnostics on frozen sera using the liquid chromatography/mass spectroscopy (LC-MS) method. Vitamin D deficiency was defined as 25 (OH) D ≤20 ng/ml. Comparisons of continuous and categorical characteristics among HIV-infected and HIV-uninfected women were made by Wilcoxon tests and Pearson chi-squared tests, respectively.
1778 women (1268 HIV+) were studied. 63% had vitamin D deficiency (60% HIV +vs. 72% HIV−; p<0.001). Multivariable predictors of Vitamin D Deficiency were being African American (AOR 3.02), Hispanic (AOR 1.40), Body mass index (AOR 1.43), Age (AOR 0.84), HIV+ (AOR 0.76), Glomerular filtration rate <90/ml/min (AOR 0.94) and WIHS site; Los Angeles (AOR 0.66), Chicago (AOR 0.63). In the HIV+ women multivariate predictors were; undetectable HIVRNA (AOR 0.69), CD4 50–200 cells/mm3 (AOR 1.60), CD4 <50 cells/mm3 (AOR 1.94) and recent Protease Inhibitor use (AOR 0.67).
In this study of over 1700 women in the US, most women with or without HIV infection had low vitamin D levels and African American women had the highest rates of Vitamin D deficiency. An understanding of the role that vitamin D deficiency plays in non-AIDS related morbidities is planned for investigation in WIHS.
Vitamin D; Vitamin D Deficiency; HIV infected; HIV uninfected
Background and methods
Achieving high adherence to antiretroviral therapy for human immunodeficiency virus (HIV) is challenging due to various system-related, medication-related, and patient-related factors. Community pharmacists can help patients resolve many medication-related issues that lead to poor adherence. The purpose of this cross-sectional survey nested within the Women’s Interagency HIV Study was to describe characteristics of women who had received pharmacist medication counseling within the previous 6 months. The secondary objective was to determine whether HIV-positive women who received pharmacist counseling had better treatment outcomes, including self-reported adherence, CD4+ cell counts, and HIV-1 viral loads.
Of the 783 eligible participants in the Women’s Interagency HIV Study who completed the survey, only 30% of participants reported receiving pharmacist counseling within the last 6 months. Factors independently associated with counseling included increased age (odds ratio [OR] 1.28; 95% confidence interval [CI] 1.07–1.55), depression (OR 1.75; 95% CI 1.25–2.45), and use of multiple pharmacies (OR 1.65; 95% CI 1.15–2.37). Patients with higher educational attainment were less likely to report pharmacist counseling (OR 0.68; 95% CI 0.48–0.98), while HIV status did not play a statistically significant role. HIV-positive participants who received pharmacist counseling were more likely to have optimal adherence (OR 1.23; 95% CI 0.70–2.18) and increased CD4+ cell counts (+43 cells/mm3, 95% CI 17.7–104.3) compared with those who had not received counseling, though these estimates did not achieve statistical significance.
Pharmacist medication counseling rates are suboptimal in HIV-positive and at-risk women. Pharmacist counseling is an underutilized resource which may contribute to improved adherence and CD4+ counts, though prospective studies should be conducted to explore this effect further.
human immunodeficiency virus; acquired immunodeficiency syndrome; antiretroviral therapy; community pharmacy; pharmacy practice; women’s health
The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.
We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women’s Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.
At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P <0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.
Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.
fracture; fragility fracture; HIV-infected women; premenopausal
Ataxia telangiectasia (AT) is a rare multisystem, neurodegenerative genetic disorder. Due to its wide clinical heterogeneity, it often leads physicians to an incorrect or missed diagnosis, and insight into this rare disease is important. Here is a case report of two cousins from the same family who showed salient characteristic features of AT along with the incidental finding of co-inheritance of hemoglobin E trait. Though both of them were from the same family, they showed differences in the type of humoral immune deficiencies, laboratory findings, and their susceptibility to develop different types of malignancies. One of them developed T cell acute lymphoblastic leukemia, isolated immunoglobulin A deficiency, and normal serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA 19.9) levels. He expired at the age of nine years. The other, though a year older, has still got normal blood counts, normal immunoglobulin levels, and elevated serum CEA and CA 19.9 levels. Thus, insight into this disease is very important as AT patients require protection from unnecessary exposure to ionizing radiation to prevent malignancies. Diagnosis of AT allows appropriate genetic counseling for the family.
Ataxia telangiectasia; hemoglobin E; T cell acute lymphoblastic leukemia; humoral immunodeficiency
To investigate rates and predictors of change in bone mineral density (BMD) in a cohort of aging men with or at risk for HIV infection.
Prospective cohort study among 230 HIV-infected and 159 HIV-uninfected men aged ≥49 years.
Longitudinal analyses of annual change in BMD at the femoral neck, total hip and lumbar spine.
At baseline 46% of men had normal BMD, 42% had osteopenia, and 12% had osteoporosis. Of those men with normal BMD, 14% progressed to osteopenia and 86% continued to have normal BMD. Of the men initially with osteopenia, 12% progressed to osteoporosis, and 83% continued to have osteopenia. Osteopenia incidence per 100 person-years at risk (PYAR) was 2.6 for HIV-uninfected men and 7.2 for HIV-infected men; osteoporosis incidence was 2.2/100 PYAR among men with osteopenia, regardless of HIV status. In multivariable analysis of annual change in BMD at the femoral neck, we found a significant interaction between heroin use and AIDS diagnosis, such that the greatest bone loss occurred with both AIDS and heroin use (adjusted predicted mean annual bone loss 0.0196 gm/cm2). Hepatitis C virus seropositivity was also associated with femoral neck bone loss (p=.04). The interaction between AIDS and heroin use also was associated with bone loss at the total hip, as was current methadone use (p<.01).
We found an association of heroin use and AIDS with BMD change, suggesting that heroin users with AIDS may be at particular risk for bone loss.
osteopenia; osteoporosis; bone mineral density; HIV; men; aging
South Africa has a high tuberculosis (TB)-human immunodeficiency virus (HIV) coinfection rate of 73%, yet only 46% of TB patients are tested for HIV. To date, relatively little work has focused on understanding why TB patients may not accept effective services or participate in programs that are readily available in healthcare delivery systems. The objective of the study was to explore barriers to and facilitators of participation in HIV counseling and testing (HCT) among TB patients in the Free State Province, from the perspective of community health workers and program managers who offer services to patients on a daily basis. These two provider groups are positioned to alter the delivery of HCT services in order to improve patient participation and, ultimately, health outcomes.
Group discussions and semistructured interviews were conducted with 40 lay counselors, 57 directly observed therapy (DOT) supporters, and 13 TB and HIV/acquired immune deficiency syndrome (AIDS) program managers in the Free State Province between September 2007 and March 2008. Sessions were audio-recorded, transcribed, and thematically analyzed.
The themes emerging from the focus group discussions and interviews included four main suggested barrier factors: (1) fears of HIV/AIDS, TB-HIV coinfection, death, and stigma; (2) perceived lack of confidentiality of HIV test results; (3) staff shortages and high workload; and (4) poor infrastructure to encourage, monitor, and deliver HCT. The four main facilitating factors emerging from the group and individual interviews were (1) encouragement and motivation by health workers, (2) alleviation of health worker shortages, (3) improved HCT training of professional and lay health workers, and (4) community outreach activities.
Our findings provide insight into the relatively low acceptance rate of HCT services among TB patients from the perspective of two healthcare workforce groups that play an integral role in the delivery of effective health services and programs. Community health workers and program managers emphasized several patient- and delivery-level factors influencing acceptance of HCT services.
Protective role of Gycyrrhiza glabra rhizomes (roots) at three dose levels (100, 75, & 50 mg/kg/bw) against sublethaldose (300 mg/kg/bw) of acetaminophen (paracetamol) induced hepatorenal damage has been assessed in mice. Parameters of study were glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), billirubin, alkaline phosphatase (ALP) as liver function tests, creatinine and urea as kidney function tests and histology for pathology. G.glabra could antagonize acetaminophen induced both,hepato and nephrotoxicity in dose dependent manner. No protection provided by a single dose of G.glabra (1.5 gm/kg/bw) against lethal dose of acetaminophen (1gm/kg/bw). Probable protective role is discussed.
Glycyrrhiza glabra; acetaminophen /paracetamol; liver-kidney; mice; antioxidants
To assess the relationships between HIV transmission risk behaviours, HIV serostatus and knowledge of HIV serostatus among active injection drug users (IDUs) residing in Tallinn, Estonia, we conducted HIV testing and administered a standardized interview to 266 participants reporting recent injection drug use. In total, 45% were HIV positive, and of those, 39% knew their HIV serostatus. Those who knew their HIV-positive serostatus were less likely to report giving someone else their needle after they used it (9%) than were HIV-negative participants (23%) and those who were HIV positive but unaware of their HIV-positive serostatus (25%). There were no statistically significant differences in unprotected sex or other drug use behaviours between the groups. Most participants reported that HIV can be transmitted through sharing needles (98%) and unprotected sexual activity (93%). Prevention needs of IDUs in this area include increasing the rates of HIV testing and implementing effective programmes to reduce sexual and drug use risk behaviours.
HIV; substance abuse; intravenous; sexual behaviour; Baltic states
Objective. To assess adherence to and acceptability of the diaphragm among 140 female sex workers in Kenya in a 6-month prospective study. Methods. At baseline and bimonthly visits, participants were interviewed on diaphragm knowledge, attitude, and practices. We used principal component analysis and logistic regression to identify predictors of consistent use. Results. At 50% of 386 bimonthly visits, women reported consistently using a diaphragm with all partners during the preceding 2 weeks. Consistent use was significantly higher at the 6-month than the 2-month visit. Women reported less covert use with “helping” (regular sex partners to whom she could go for help or support) than with “other” partners. Perceptions that diaphragms are easier to use than condoms and that their lack of coital interruption is important were associated with consistent diaphragm use with both partner types. Partner support of diaphragm use is correlated with consistent use with “helping” partners only while higher parity, consistent condom use, and perceived lack of need of condoms as a benefit of diaphragms were associated with consistent use with “other” partners. Conclusions. Diaphragm acceptance among female sex workers in Nairobi was high. Future studies should distinguish between partner types when evaluating diaphragm adherence.
To assess whether complementary and alternative medicine (CAM) use is associated with the timing of highly active antiretroviral therapy (HAART) initiation among human immunodeficiency virus (HIV)–infected participants of the Women’s Interagency HIV Study.
Prospective cohort study between January 1996 and March 2002. Differences in the cumulative incidence of HAART initiation were compared between CAM users and non–CAM users using a logrank test. Cox regression model was used to assess associations of CAM exposures with time to HAART initiation.
Main Outcome and Exposures
Study outcome was time from January 1996 to initiation of HAART. Primary exposure was use of any CAM modality before January 1996, and secondary exposures included the number and type of CAM modalities used (ingestible CAM medication, body practice, or spiritual healing) during the same period.
One thousand thirty-four HIV-infected women contributed a total of 4987 person-visits during follow-up. At any time point, the cumulative incidence of HAART initiation among CAM users was higher than that among non–CAM users. After adjustment for potential confounders, those reporting CAM use were 1.34 times (95% confidence interval: 1.09, 1.64) more likely to initiate HAART than non–CAM users.
Female CAM users initiated HAART regimens earlier than non–CAM users. Initiation of HAART is an important clinical marker, but more research is needed to elucidate the role specific CAM modalities play in HIV disease progression.
To investigate the relationship between HIV infection and childbearing before and after the availability of HAART.
Enrollment in the Women’s Interagency HIV Study took place in 1994–1995 (pre-HAART era), and again in 2001–2002 (HAART era). Live birth rates prior to enrollment were compared between treatment era cohorts for HIV-infected and HIV-uninfected women aged 15–44 years using Poisson regression. For HIV-infected women we included live births between HIV diagnosis date and study entry; the HAART era cohort included only women diagnosed with HIV in 1996 and after.
Among HIV-infected women, the HAART era live birth rate was 150% higher than in the pre-HAART era (p=.001), vs. a 5% increase among HIV-uninfected women. The rate of increase in live birth rate was higher for women ≥35 years (vs. <25, p=.02), and with >high school education (vs.
The availability of effective therapeutic interventions has profoundly impacted childbearing among HIV-infected women.
HIV; women; reproductive decision-making; birth rate; highly active antiretroviral therapy
The present study revealed significantly lower levels of serum magnesium in patients with preterm labour without any apparent cause as compared to normal term pregnant women in labour. The values were also lower in women with low socioeconomic status, older age and consuming vegetarian diet. Hence, estimation of serum magnesium levels in pregnancy may be a useful parameter in preterm labour.
Magnesium; preterm labour; socioeconomic status; diet
Results 1-18 (18)
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