Rate and Predictors of Ineffective HIV Protection in African Men Who Have Sex with Men Taking Pre-Exposure Prophylaxis

AIDS and Behavior - We investigated the rate and predictors of ineffective HIV protection in men who have sex with men (MSM) taking pre-exposure prophylaxis (PrEP) in a prospective cohort study...     

Interaction between theophylline and oestrogen in the rat uterus

Theophylline alone or in the presence of 0.001, 0.01, 0.1 or 1 microgram oestradiol-17 beta/100 g body wt increase uterine RNA and protein content 6 h after administration. Uterine oedema induced by physiological doses of oestradiol-17 beta was increased further in the presence of theophylline. Theophylline decreased the number of eosinophils in the blood and concurrently decreased oestrogen-induced uterine oesinophilia at doses of 0.01, 0.1, 1, 10 or 30 micrograms oestradiol-17 beta/100 g body wt. Oestrogen binding by uterine eosinophils in vitro increased in the presence of theophylline. This effect of theophylline could explain the increase of oestrogen-induced uterine oedema in vivo.     

Prostate-specific membrane antigen (PSMA)-mediated laminin proteolysis generates a pro-angiogenic peptide

Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase expressed in a number of tissues. PSMA participates in various biological functions depending on the substrate available in the particular tissue; in the brain, PSMA cleaves the abundant neuropeptide N-acetyl-aspartyl-glutamate to regulate release of key neurotransmitters, while intestinal PSMA cleaves polyglutamated peptides to supply dietary folate. PSMA expression is also progressively upregulated in prostate cancer where it correlates with tumor progression as well as in tumor vasculature, where it regulates angiogenesis. The previous research determined that PSMA cleavage of small peptides generated via matrix metalloprotease-mediated proteolysis of the extracellular matrix protein laminin potently activated endothelial cells, integrin signaling and angiogenesis, although the specific peptide substrates were not identified. Herein, using enzymatic analyses and LC/MS, we unequivocally demonstrate that several laminin-derived peptides containing carboxy-terminal glutamate moieties (LQE, IEE, LNE) are bona fide substrates for PSMA. Subsequently, the peptide products were tested for their effects on angiogenesis in various models. We report that LQ, the dipeptide product of PSMA cleavage of LQE, efficiently activates endothelial cells in vitro and enhances angiogenesis in vivo. Importantly, LQE is not cleaved by an inactive PSMA enzyme containing an active site mutation (E424S). Endothelial cell activation by LQ was dependent on integrin beta-1-induced activation of focal adhesion kinase. These results characterize a novel PSMA substrate, provide a functional rationale for the upregulation of PSMA in cancer cells and tumor vasculature and suggest that inhibition of PSMA could lead to the development of new angiogenic therapies.     

Adrenal rest tumor of the liver causing Cushing's syndrome: treatment with ketoconazole preceding an apparent surgical cure

Ketoconazole, an imidazole derivative known to inhibit cytochrome P450-dependent adrenal enzymes was given to a patient with a functioning adrenal rest tumor of the liver in preparation for surgery. The drug was administered in a stepwise manner for 42 days starting with 400 mg and reaching 1 g the last 4 weeks of the trial. Clear clinical improvement was evident early in the trial and was associated with evidence of amelioration of her hypercortisolism and striking changes in serum and urinary levels of steroid hormones and metabolites. Sex steroids in serum and urine fell dramatically from the first day to the end of the trial. Urinary 17-ketosteroid excretion fell from a basal average of 139 mg/24 h to near normal levels within a week of therapy; serum testosterone fell from a basal level of 2.4 to 0.18 ng/ml; serum 17 beta-estradiol fell likewise from 1096 to 150 pg/ml. In contrast, cortisol levels in serum and urine increased in the first 2 weeks of the trial and subsequently fell to values below the basal levels. Similarly, serum 17 alpha-OH-progesterone levels increased 63% above the basal levels by day 6 of the trial and declined afterwards. Nine months after successful tumor resection the patient is apparently cured as judged by steroid hormone levels and physical appearance. We conclude that ketoconazole was effective in blocking tumoral steroidogenesis which resulted in clinical benefit.     

Incidence and factors influencing on Helicobacter pylori infection recurrence.

OBJECTIVES: a) To determine the rate of H. pylori reinfection after successful eradication in a 4-year follow-up study; and b) To evaluate the contribution of different factors in the infection relapse. PATIENTS AND METHODS: A total of 208 patients (age range 18-81 years; average 50 years; 87 women) who had been successfully treated for H. pylori infection were included. Annually, urea breath test was assessed to determine H. pylori status after eradication. Age, sex, rural/urban environment, smoking habit, treatment regimens against H. pylori and urea breath test values were evaluated. Results: reinfection occurred in 9,6% of patients observed, 6,7% (14/208) in the first year, 1,9% (4/208) in the second year, 1% (2/208) in the third and 0% in the forth. Risk factors for infection recurrence were younger age and higher values of urea breath test in the multivariante analysis. CONCLUSIONS: annual reinfection rate was 2,4 pacients-year. Younger patients and higher values of urea breath test were factors associated with a higher rate of reinfection relapse. Annually, urea breath test should be performed to detect reinfection in order to avoid ulcer complications.     

Clinical, endoscopic, and functional studies in 408 patients with Barrett's esophagus, compared to 174 cases of intestinal metaplasia of the cardia

OBJECTIVE: The pathophysiology of gastroesophageal reflux disease (GERD) has been studied extensively in patients with long-segment Barrett's esophagus (LSBE), but few reports have explored GERD pathophysiology in patients who have short-segment Barrett's esophagus (SSBE) or intestinal metaplasia at the cardia (IMC). We aimed to compare clinical, endoscopic, histological, and functional features in patients with LSBE, SSBE, and IMC. METHODS: We identified 582 patients who had intestinal metaplasia at the squamocolumnar junction in the distal esophagus and divided them into three groups based on the extent of columnar-lined esophagus observed endoscopically: 1) patients with IMC who had no columnar-lined esophagus (i.e., the squamocolumnar and gastroesophageal junctions coincided), 2) patients with LSBE who had >3 cm of columnar-lined esophagus, and 3) patients with SSBE who had <3 cm of columnar-lined esophagus. All patients had esophageal manometric evaluation, and 24-h esophageal pH monitoring was performed to determine the extent of acid and bile (bilirubin) reflux. RESULTS: There were 174 patients with IMC, 155 with LSBE, and 25 with SSBE. Compared to patients with LSBE and SSBE, patients with IMC had significantly lower frequencies of GERD symptoms, hiatal hernia, and erosive esophagitis; significantly higher lower esophageal sphincter pressures; and significantly shorter durations of acid and bile reflux. Between patients with SSBE and LSBE, significant differences were found in the frequency of hiatal hernia and duration of acid reflux (both greater in the patients with LSBE). Also, dysplasia was significantly more frequent in patients with LSBE than in those with SSBE or IMC. CONCLUSION: GERD symptoms, signs, and physiological abnormalities are found more often in patients with Barrett's esophagus than in those with IMC, and the duration of acid reflux in patients with LSBE is greater than that in patients with SSBE. These findings suggest that the extent of intestinal metaplasia in the esophagus is related directly to the severity of underlying GERD.     

Influenza vaccination status in multiple sclerosis patients from Latin America

Journal of NeuroVirology - The objective of the present study was to identify the frequency of MS patients in Latin America (LATAM) that received the influenza vaccine during the most recent season...     

Regulation of neuroinflammation by B cells and plasma cells

The remarkable success of anti‐CD20 B cell depletion therapies in reducing the burden of multiple sclerosis (MS) disease has prompted significant interest in how B cells contribute to neuroinflammation. Most focus has been on identifying pathogenic CD20⁺ B cells. However, an increasing number of studies have also identified regulatory functions of B lineage cells, particularly the production of IL‐10, as being associated with disease remission in anti‐CD20–treated MS patients. Moreover, IL‐10–producing B cells have been linked to the attenuation of inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. In addition to IL‐10–producing B cells, antibody‐producing plasma cells (PCs) have also been implicated in suppressing neuroinflammation. This review will examine regulatory roles for B cells and PCs in MS and EAE. In addition, we speculate on the involvement of regulatory PCs and the cytokine BAFF in the context of anti‐CD20 treatment. Lastly, we explore how the microbiota could influence anti‐inflammatory B cell behavior. A better understanding of the contributions of different B cell subsets to the regulation of neuroinflammation, and factors that impact the development, maintenance, and migration of such subsets, will be important for rationalizing next‐generation B cell–directed therapies for the treatment of MS.     

Comparison of the primary stability of orthodontic miniscrews after repeated insertion cycles:: An in vitro study

ObjectivesTo compare the primary stability of miniscrews after repeated cycles of insertion through insertion torque (IT) measurements and resonance frequency analysis (RFA).Materials and MethodsSixty titanium miniscrews were divided into two groups according to the insertion protocol: one with predrilled sites and the other self-drilled into porcine iliac crest bone specimens. Each group had three cycles of reinsertion. After each insertion, the IT and RFA were measured. The IT was measured by using a torque meter, and the RFA was measured using the Osstell ISQ device. A total of five miniscrews of each group were selected for sequential assessment of the morphology of their tip and threads using scanning electron microscopy after each insertion cycle.ResultsNo statistically significant differences were found in the IT values of miniscrews reinserted up to three times in the group with predrilled surgical sites. The IT value increased significantly with the number of reinsertions in the self-drilled group. The RFA value decreased as the number of insertions increased in both groups.ConclusionsUnder the conditions of this in vitro study, reinserting miniscrews deteriorates the integrity of their tip and thread. Reinsertion should be discouraged particularly when insertion sites are not predrilled.