Elimination of high-risk human papillomavirus type HPV16 infection by ‘Praneem’ polyherbal tablet in women with early cervical intraepithelial lesions

Purpose

‘Praneem’, a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16.

Methods

Twenty women molecularly diagnosed positive for HPV16 infection without or with low grade squamous intraepithelial lesion (LSIL) or inflammation were assigned to receive intra-vaginal, topical application of either Praneem tablet or placebo for 30 days excluding the days of menstrual period and were evaluated for persistence of HPV infection using HPV L1 consensus and HPV type 16-specific PCR as primary outcome.

Results

One course of Praneem treatment resulted in elimination of HPV in 6 out of 10 (60%) cases. A repeat treatment of four patients with persisting HPV infection resulted in clearance of HPV in two additional cases resulting in an overall 80% clearance of HPV 16 as against a spontaneous clearance of 10% (1/10) seen in the placebo arm. The elimination of HPV DNA was found to be accompanied by marked improvement in clinical symptoms and cytological abnormalities of Praneem-treated patients.

Conclusion

Our results showed for the first time that a 30-day intra-vaginal application of the Praneem can result in elimination of HPV infection from the uterine cervix.     

A profile of clients of male sex workers in Córdoba, Argentina

This paper provides a profile of clients seen by male sex workers (MSWs) in Córdoba, Argentina. Thirty-two MSWs completed a diary after each paid sexual encounter with a client over a two-week period. The results show that 254 commercial sex encounters were reported. More than half of these encounters were with first time clients. The most common source of recruiting clients was advertisements followed by street contact. The majority of the clients were aged in their 30s or 20s, and identified as 'middle class' and 'bisexual' or 'gay'. In the majority of the encounters, alcohol or drugs were not used by clients, and in about less than half of the cases, the MSWs had some personal tracing information about the client. Most of the clients indicated to the MSW what sexual activity they wanted and unsafe anal sex was requested in a minority (6%) of the encounters. While most workers reported having no or little attraction to the client, most indicated that they would serve the client again. The implications of the results for public health education and further research are discussed.     

The relationship between second-hand smoke and wheezing in infants from Córdoba,Argentina

BackgroundWheezing constitutes a common respiratory symptom in children, and several risk factors have been associated with the prevalence of recurrent wheezing (RW) and its severity, especially viral respiratory infections and second-hand smoke (SHS) exposure.ObjectiveTo analyze the relationship between smoking patterns in the home and wheezing, in infants from the city of Córdoba, Argentina, during their first year of life.MethodsParents of infants were invited to complete a standardized questionnaire voluntarily and anonymously (WQ-P1-EISL). Wheezing in the first 12 months of life was classified as occasional wheezing (OW) when having one or two episodes during the first 12 months of life; recurrent wheezing (RW) if having three or more, and more frequent wheezing (MFW) ≥6 episodes.Results409 infants (39.0%) had one or more episodes of wheezing in the first 12 months. Of these, 214 infants (52.3%) presented occasional wheezing (OW), 135 (33%) had recurrent wheezing (RW), and 60 (14.7%) more frequent wheezing (MFW). SHS was significantly related to MFW, especially if the mother smoked (OR = 2.7; IC 95%: 1.4–5.18; p = 0.0009) or if she smoked during pregnancy (OR = 4; IC 95%: 1.8–8.5; p = 0.0001). This group of MFW was also associated with SHS as well as having been to the emergency room for wheezing (40.87%, p = 0.0056).ConclusionThe results indicate that second-hand tobacco smoke is a significant risk factor for the presence of wheezing in infants, and for its severity. Our findings have significant implications for public health, as smoking is a modifiable behavior.     

High ulcerative colitis and Crohn's disease ratio in a population-based registry from Córdoba,Argentina

BackgroundFew studies have described the epidemiology and clinical behavior of inflammatory bowel disease (IBD) in South America. The aim of this study was to report on the prevalence, phenotype, and treatment of patients with IBD diagnosis in Capital Department of the Province of Córdoba, Argentina.MethodsData from adult patients (≥ 18 years-old) with IBD diagnosis that attended 12 public or private centers between 05/2014 and 05/2019 were included in a common registry.ResultsA total of 655 patients were included (females: 53.4%). The ratio of ulcerative colitis (UC) (n = 561) to Crohn's disease (CD) (n = 88) was 6.38, with age-adjusted IBD prevalence being 70.1 (95% confidence interval 70.08–70.12) cases/100,000 habitants. Extraintestinal manifestations were diagnosed in 22.8% of patients, and left-side colitis (46%) was the most frequent extension in UC patients. In CD patients, colonic involvement (55.7%) and non-stricturing/non-penetrating behavior (74%) were the most frequent presentations. Biologic therapy was used in 36.4% of CD patients and 9.1% of UC patients (P<0.001).ConclusionIn this population registry study, IBD prevalence was similar to that reported in other series in the region. A higher UC/CD ratio was observed due to the lower prevalence of CD compared to similar studies in South America.     

Risk factors for recurrent wheezing in the first year of life in the city of Córdoba,Argentina

BackgroundWheezing is a very common respiratory symptom in infants. The prevalence of wheezing in infants, conducted in developed countries shows prevalence rates ranging between 20% and 30%. However, we do not know the risk factors in our population of wheezing infants.MethodsA standardised written questionnaire (WQ-P1-EISL) in infants between 12 and 18 months of age residing in the city of Cordoba was used; population/sample included 1031 infants. Recurrent wheezing (RW) was defined as three or more episodes of wheezing reported by the parents during the first 12 months of life. Data obtained were coded in Epi-Info™ (version 7) and statistically analysed with SPSS (version 17.5) software in Spanish. Parametric tests (one-way ANOVA) were performed for identifying significantly associated variables.ResultsThe prevalence of wheezing infants was 39.7%; recurrent wheezing 33%; and severe wheezing 14.7%; 13.7% had pneumonia before the first year and of these 6.3% were hospitalised, multiple variables as risk factors for wheezing were found such as: >6 high airway infections and bronchiolitis in the first three months of life, smokers who smoke in the home among other risk factors and protective factors in those who have an elevated socioeconomic status.ConclusionIt is known that persistent respiratory problems in children due to low socioeconomic status is a risk factor for wheezing, pneumonia and could be a determining factor in the prevalence and severity of RW in infants. Research suggests that there are areas for improvement in the implementation of new educational strategies.     

Anogenital warts contributing to the risk of squamous intraepithelial lesions among HIV-positive women of São Paulo,Brazil

Unsafe sexual practices may expose HIV-positive women to high-grade squamous intraepithelial lesions (SIL) and to infection with oncogenic human papillomavirus (HPV) types. A cross sectional study of 141 HIV-positive women was designed to evaluate risk factors for the development of cervico-vaginal SIL and HPV-DNA detection/typing. Uni- and multivariate forward stepwise analysis was used to determine the relationship between risk variables and HPV infection and between risk behaviour, HPV and HIV infection with development of SIL. Univariate analysis showed that HPV-DNA infection was related to previous and recurrent anogenital warts, male genital warts and cytological alteration. For final multivariate analysis, both HPV type (undetermined- and high-risk, OR=29.3 and 112.0, respectively) were statistically associated (P=0.019) with high-grade cervico-vaginal SIL. The presence of anogenital warts as well as high- and undetermined-risk HPV infection may alert to cyto/histopathological alterations. These results point out the importance of the use of barrier methods and routine early genitoscopy/treatment for HIV-infected partners.     

Relationship between human papillomavirus (HPV) genotyping and genital neoplasia in HIV-positive patients of Santos City, São Paulo, Brazil

Among HIV-positive women, infection with multiple human papillomavirus (HPV) types is known to be more frequent and persistent, as well as a greater prevalence of high-grade genital lesions. This study aims to characterize, for the first time in Brazil, HPV presence and types among HIV-positive women of a high-risk population for genital intraepithelial neoplasia (GIN) development. A non-anonymous, voluntary, cross-sectional epidemiological survey was conducted, from June 1996 to April 1997, among 141 HIV-positive women followed at the Center of Reference in AIDS (CRAIDS). They were submitted to gynaecological examination, cytological screening and biopsies whenever necessary, for GIN and HPV DNA detection through polymerase chain reaction (PCR) technique. Positive HPV DNA were found in 80.8% patients. Two or more HPV types were detected in 45% of the samples. The most frequent HPV types detected were 16, 18 (30.5%); 61, 53 (24.4%), and non-identified types (18.7%). According to the oncogenic potential, 34.8% were considered of high-risk types. Among these HIV-positive patients, a great variety of HPV types, including high-risk types, was found in anogenital environment, as well as among young women, a great prevalence of high-grade genital lesions. Thus, it should strengthen the need for a periodical careful gynaecological examination among those women.     

Microgeographic Genetic Variation of the Malaria Vector Anopheles darlingi Root (Diptera: Culicidae) from Córdoba and Antioquia,Colombia

Anopheles darlingi is an important vector of Plasmodium spp. in several malaria-endemic regions of Colombia. This study was conducted to test genetic variation of An. darlingi at a microgeographic scale (approximately 100 km) from localities in Córdoba and Antioquia states, in western Colombia, to better understand the potential contribution of population genetics to local malaria control programs. Microsatellite loci: nuclear white and cytochrome oxidase subunit I (COI) gene sequences were analyzed. The northern white gene lineage was exclusively distributed in Córdoba and Antioquia and shared COI haplotypes were highly represented in mosquitoes from both states. COI analyses showed these An. darlingi are genetically closer to Central American populations than southern South American populations. Overall microsatellites and COI analysis showed low to moderate genetic differentiation among populations in northwestern Colombia. Given the existence of high gene flow between An. darlingi populations of Córdoba and Antioquia, integrated vector control strategies could be developed in this region of Colombia.     

The prevalence of high-risk HPV infection in pregnant women from Morelos, México

OBJECTIVE: Some studies suggest the possibility that the physiological process of pregnancy modifies certain characteristics of the mother, increasing the risk of both, infection and persistence of infection with HPV. This association, however, has not been firmly established. This study seeks to determine the prevalence of oncogenic HPV infecton in a sample of pregnant Mexican women and its possible risk factors. MATERIAL AND METHODS: A cross-sectional study was conducted using a sample of 274 pregnant women sought first level of care services during the year 2000 at the antenatal clinic of the Mexican Institute of Social Security (IMSS) in Cuernavaca, Morelos, Mexico. Samples of vaginal cells were obtained through self-collected specimens, for the high-risk HPV DNA test using the Hybrid Capture 2 test (HC2). A structured questionnaire was administered regarding sociodemographic, gynecologic, obstetric and sexual behavior characteristics. RESULTS: The mean age was 25.7 years. The average time of pregnancy when the study was conducted was 6 months. The principal risk factors associated with high-risk HPV infection were: ages between 20 and 29 (OR= 2.82; CI 95% 1.02-7.76)), age 30 and over (OR= 6.85,CI 95% 1.22-38.2); partners having sexual relations with other partners (OR= 2.05; CI 95% 1.2-3.7)); schooling less than 6 years (OR= 1.68 CI 95% 0.7-4.3); number of lifetime sexual partners > 2 (OR= 1.54 CI 95% 0.7-3.4); and current smoking (OR= 1.6 CI 95% 0.6-5.0). CONCLUSIONS: Our findings show a higher prevalence of high-risk HPV infection in pregnant women, more than double, that reported in studies of non-pregnant women. The associated risk factors are similar to those of the non-pregnant population. Follow-up in these women is recommended in order to evaluate the persistence or regression of the infection.     

Over-expression of protein kinase C isoforms (α, δ, θ and ζ) in squamous cervical cancer

Protein kinase C was found to be significantly over-expressed in cancer samples compared to adjacent normal cervical tissues by proteomics in our previous study. The aim of this study was to examine protein kinase C expression and to analyze the expression patterns of protein kinase C isoforms in squamous cervical cancer at the protein levels and their associations with clinical and pathologic factors of squamous cervical cancer. First, Western blotting was used to examine protein kinase C expression in the specimens of tumors and matched adjacent normal tissues which were collected from 12 patients with squamous cervical cancer. Protein kinase C isoforms (α, δ, θ and ζ) expression were then detected by immunohistochemistry in other 43 cases of squamous cervical cancer tissues, 32 cases of corresponding adjacent normal cervical squamous epithelial tissue and 31 cases of cervical intraepithelial neoplasia. Western blot analysis revealed that protein kinase C expression was positive in squamous cervical cancer while it was not expressed in normal cervical tissues. On the other hand, immunohistochemical analysis suggested that, protein kinase C isoforms (α, δ, θ and ζ) expression was significantly higher in squamous cervical cancer compared to cervical intraepithelial neoplasia, as well as in cervical intraepithelial neoplasia compared with normal tissues, respectively.High levels of protein kinase C α expression were associated with cellular differentiation(P<0.05). Protein kinase C δ was significantly associated with tumor stage (P<0.05) and protein kinase C ζ was associated with lymphatic metastasis (P < 0.05). These findings indicate that protein kinase C isoforms expression in cervical lesions was associated with carcinogenesis and might play important roles throughout the process of cervical cancer development.     

Lack of indinavir-associated nephrological complications in HIV-infected adults (predominantly women) with high indinavir plasma concentration in Abidjan, Côte d'Ivoire

To report the tolerance of indinavir combined with ritonavir (IDV/r 800/100 mg) twice daily (bid) in sub-Saharan African HIV-infected adults. HAART-naives patients started zidovudine plus lamivudine plus IDV/r 800/100 mg bid. Follow-up included standardized documentation of morbidity, CD4(+) cell count, creatininemia, plasma HIV-1 RNA, and IDV minimal plasma concentration (C(min)) measurements at month 1 (M1), M3, and M6. Seventy HIV-1-infected adults (68 women, median CD4 235/mm(3)) started HAART. At M6, 63% had undetectable viral load, and the median gain in CD4 since baseline was +128/mm(3). During the first 6 months, 21 patients experimented with 23 treatment modifications (reduction in IDV/r 400/100 mg bid, n = 11; switch to efavirenz, n = 11; zidovudine replaced by stavudine, n = 1), including 22 for digestive intolerance and 1 for severe anemia. At M1, M3, and M6, 67, 59, and 48 patients were still receiving IDV/r 800/100 mg bid, of whom 70%, 72%, and 60% had IDV Cmin above 5 ng/ml, respectively. In these patients, at M1, M3, and M6, the mean (+/- SD) IDV C(min) were 3431 +/- 3835 ng/ml, 2288 +/- 2116 ng/ml, and 1543 +/- 2398 ng/ml, respectively. There was no renal insufficiency of any grade, and no symptoms of urinary stones. The IDV/r 800/100 mg bid-containing regimen led to high IDV Cmin and a high rate of digestive intolerance. There was a surprising lack of nephrological side effects during the 6 months of follow-up, supporting the hypothesis that nephrological tolerance of IDV might be higher in sub-Saharan African individuals than in Americans or Europeans.     

Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts “in vitro”

We examined the effects of polyarticular juvenile idiopathic arthritis (pJIA) serum on proliferation, differentiation, mineralization, and apoptosis of human osteoblast cells (hOb) in culture. The hOb were cultured with 10% serum from active pJIA and healthy controls (CT) and were tested for DNA synthesis, alkaline phosphatase (AP) activity, osteocalcin (OC) secretion, calcium levels, caspase 3 activity, and DNA fragmentation. None of the patients had used glucocorticoids for at least 1 month before the study, or any other drug that can affect bone mineral metabolism. Human inflammatory cytokine levels (IL-6, IL-8, IL-10, IL-1β, TNF-α, and IL-12p70) were measured in pJIA and CT sera. Low levels of AP activity was observed in pJIA cultures compared with CT cultures (67.16 ± 53.35 vs 100.11 ± 50.64 μmol p-nitrophenol/h⁻¹ mg⁻¹ protein, P = 0.008). There was also a significant decrease in OC secretion (9.23 ± 5.63 vs 12.82 ± 7.02 ng/mg protein, P = 0.012) and calcium levels (0.475 ± 0.197 vs 0.717 ± 0.366 mmol/l, P = 0.05) in pJIA hOb cultures. No difference was observed in cell proliferation (323.56 ± 108.23 vs 328.91 ± 88.03 dpm/mg protein, P = 0.788). Osteoblasts cultured with JIA sera showed lower levels of DNA and increased fragmentation than osteoblasts cultured with CT sera. pJIA sera showed higher IL-6 values than CT (21.44 ± 9.31 vs 3.58 ± 2.38 pg/ml, P < 0.001), but no difference was observed related to IL-8, IL-10, IL-1β, TNF-α, and IL-12p70 between pJIA and controls. This study suggests that serum from children with pJIA inhibits differentiation, mineralization and may increase apoptosis of hOb cultures, and inflammatory cytokines such as IL-6 might be a mechanism in this find. These results may represent an alternative therapeutic target for prevention and treatment of bone loss in JIA.     

The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome

BACKGROUND: Increased levels of B lymphocyte stimulator (BLyS) have been detected in serum from patients with systemic lupus erythematosus and rheumatoid arthritis. OBJECTIVE: To determine the level of BLyS in serum from patients with primary's Sj?gren's syndrome (SS), another autoimmune disease in which B cell activation is high. METHODS: Serum samples from 49 patients with primary SS according to the revised European criteria were assayed for BLyS, quantitative immunoglobulins, and autoantibody levels and compared with samples from 47 healthy control subjects. RESULTS: The median level of BLyS was 5.99 ng/ml (25th-75th centile range 3.20-8.93 ng/ml) in SS v 2.49 ng/ml (25th-75th centile range 1.96-2.96 ng/ml) in healthy controls (p<0.001). More importantly, among patients with SS, the presence of anti-SSA antibodies was associated with significantly higher levels of BLyS (medians 7.90 ng/ml v 3.70 ng/ml; p=0.008) as was the presence of anti-SSB antibodies (medians 7.14 ng/ml v 3.70 ng/ml; p=0.02) and of rheumatoid factor (medians 7.70 ng/ml v 3.80 ng/ml; p=0.016). The level of BLyS in three patients with a monoclonal gammopathy was higher than in the other patients (medians 26.53 ng/ml v 5.92 ng/ml; p=0.13). Higher levels of BLyS were associated with higher levels of gammaglobulins and IgG. There was a strong correlation between BLyS and rheumatoid factor level (r=0.71, p<0.0001), anti-SSA IgG level (r=0.32, p=0.02) and anti-SSA IgM level (r=0.39, p=0.006). CONCLUSION: In human SS the level of BLyS correlates with the level of autoantibodies. Thus, BLyS may play a part in activating specific autoreactive B cells and modulating the level of production of autoantibodies which are the hallmark of the disease. These findings raise the possibility of a novel therapeutic approach in human SS.