Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites

BACKGROUND & AIMS: The critical role of cyclooxygenase (COX) products in maintenance of renal function in cirrhosis with ascites discourages the use of nonsteroidal anti-inflammatory drugs in this disease. The recent development of selective COX-2 inhibitors opens new avenues for the use of these compounds in decompensated cirrhosis. The current study evaluates the effects of a selective COX-2 inhibitor (SC-236) on renal function in cirrhotic rats with ascites. METHODS: In protocol 1, urine volume, urinary excretion of sodium and prostaglandins, glomerular filtration rate, and renal plasma flow were measured before and after administration of SC-236 (n = 12) or ketorolac (n = 10) to rats with cirrhosis. Protocol 2 was aimed at assessing the effects of COX inhibitors on renal water metabolism in 28 cirrhotic rats. RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism. CONCLUSIONS: These findings indicate that SC-236 does not significantly impair renal function in rats with cirrhosis.     

Simultaneous presence of blaTEM and blaSHV genes on a large conjugative plasmid carried by extended-spectrum beta-lactamase-producing Klebsiella pneumoniae

BACKGROUND: Among members of the family Enterobacteriaceae, the production of plasmid-mediated extended-spectrum beta-lactamases (ESbetaLs) has emerged as an important mechanism of the resistance to beta-lactams. METHODS: The molecular basis of extended-spectrum beta-lactamase in 48 strains of Klebsiella pneumoniae, recovered from neonatal patients with nosocomial septicemia during an outbreak that occurred in November 2000 at a Neonatal Intensive Care Unit of The Andes University Hospital in Venezuela, were investigated. RESULTS: The isolates were resistant to expanded-spectrum cephalosporins, aztreonam, gentamicin, kanamycin, tetracycline, and chloramphenicol, but remained susceptible to cefoxitin, imipenem, amikacin, and tobramycin. Production of ESbetaL activity was confirmed by restoring susceptibility to ceftazidime in the presence of clavulanic acid. All isolates harbored an 87-kilobase plasmid. Analysis of the outer membrane protein patterns did not reveal relevant changes of the porins profile. All resistance markers were transferable to Escherichia coli by conjugation and were lost en bloc after treatment with acridine orange. Isoelectric focusing for beta-lactamases was performed on transconjugants, obtaining 2 bands with isoelectric points of 5.4 and 8.2. Genes encoding both enzymes are located on the single, self-transferable 87-kilobase plasmid pKAM542. Analysis of the plasmid by hybridization revealed the presence of both blaTEM and blaSHV determinants. Cloning and sequencing identified them as blaTEM-1 and blaSHV-5, respectively; the latter was responsible for the ESbetaL activity among nosocomial isolates of K pneumoniae. CONCLUSIONS: Microbiologists, epidemiologists, and clinicians must be aware of potential ESbetaL-encoding organisms to assess proper antimicrobial managements and effective infection controls.     

Systemic lupus erythematosus in southern Spain: a comparative clinical and genetic study between Caucasian and Gypsy patients

We evaluated the influence of the hereditary make-up on the development of systemic lupus erythematosus (SLE) in two ethnic groups [Gypsy and white Caucasian Mediterranean (WCM) populations], living in the same geographic area. We compared 81 WCM and 25 Gypsy patients with SLE. The control group consisted of 185 healthy unrelated individuals, 105 WC and 80 Gypsies. In the Gypsy population, the onset of SLE occurred at earlier ages than in the other ethnic group (25.9 versus 32.0 years, P = 0.02), and showed lower SLEDAI peak values (4.9 versus 7.0, P = 0.016). The frequency of joint, kidney, gastrointestinal and eye involvement was significantly lower in Gypsy patients. In contrast, SLE-associated antiphospholipid syndrome, thrombosis and livedo reticularis were more frequent in Gypsies than in the majority ethnic group (WCM). In WCM patients, DRB1* 1303-DQB1*0301 haplotype was associated with SLE (P = 0.001, Pc = 0.038). We found SLE to be associated with DR5 (P = 0.006, Pc = 0.05) in the Gypsy population as well as a protective effect of DPB1*0401 when DR5 was not present (P = 0.008, Pc = 0.032). In conclusion, we found some clinical differences between WCM and Gypsy patients with SLE. Furthermore, HLA associations between HLA-DRB1-DQB1 and SLE were different for Gypsy people.     

Acceptability of food supplements in pregnant or lactating women and children under 5 years of age]

OBJECTIVE: The present study explores the acceptance and consumption of nutritional supplements that form part of a governmental program to support nutritionally vulnerable groups. MATERIAL AND METHODS: Pregnant and lactating women, and mothers of malnourished toddlers, infants and children were interviewed. Data were collected, after introduction with an interview guide with an open-ended format, through face-to-face interviews conducted at home. Interviews were taped with previous informed consent. Analysis included topics and subtopics approached by the interviewed women. RESULTS: The studied population showed good acceptance to the supplement when offered as a drink. When considering benefits, pregnant women thought first of their baby's health than of their own and associated the possible advantages of the supplement to its "vitamin" contents. Acceptance of the flavors was largely influenced by previous contact to specific flavors. Children under 1 year of age preferred the liquid consistency and elderly children favored the puree. Most mothers considered that the offered amount was enough and there was the general impression that, as the time of the intervention elapsed, children showed greater appetite. The diet was not substituted by the supplement. CONCLUSIONS: Acceptance of the supplement may be improved by messages focusing on the well-being and health of the child and insisting on the benefits for the pregnant mother. Community health providers should be involved in supporting the program, recommending consumption and acceptance of the supplement. The identification by mothers of "vitamins" as part of the supplement may be used to reinforce the concept of beneficial effects associated to micronutrient supplementation. Qualitative evaluations should be performed as part of the assessment of community-based programs.     

Effects of captopril on regional segment motion during acute coronary occlusion.

The effects of captopril on myocardial segment function in different degrees of transient coronary occlusion were studied using ultrasonic dimension gauges in 15 open-chest dogs. The occlusion procedures (OP) were performed on the left anterior descending coronary artery (LAD) in eight dogs and on the left circumflex coronary artery (Cx) in seven dogs. To measure the changes in segment shortening in the subendocardium we used eight dogs (ischemic and control zones: four dogs LAD and four dogs Cx). To measure the changes in wall thickening we used seven dogs (ischemic and control zones: three dogs LAD and four dogs Cx). Total coronary OP lasting 1 min and partial OP (70-80%) lasting 1 min and 2 min 30 s, before and after captopril (0.25 mg/kg i.v.) were performed. Left ventricular pressure, dP/dt, coronary flow, and ECG were monitored. Total coronary OP (1 min) changed segment shortening (18% LAD; 14% Cx) and wall thickening (19% LAD; 18% Cx) to values of dyskinesis (-3% and -4% for shortening; -6% and -5% for thickening). Captopril improved regional function maintaining positive values for shortening (4% LAD; 3% Cx) and thickening (0.3% LAD; 4% Cx). Similar responses were obtained during partial OP and captopril. Results suggest that captopril produced a significant improvement in the regional function parameters affected by ischemia both in total and partial obstructions.     

A bio-psycho-social approach to acute hypertensive disease in pregnancy

In this paper, the approach to the genesis of the acute hypertension of pregnancy, uses a conceptual and methodological perspective adjusted to its multifactorial nature; a set of questions with epidemiologic focus is proposed, in order to vinculate psychosocial factors with the biologic processes characteristic of this health problem.     

p16INK4A and p15INK4B gene deletions in primary leukemias

The 9p21 locus has been deleted at a high frequency in a wide variety of tumors. Recently, two genes, p16INK4A and p15INK4B (also called MTS1 and MTS2), have been localized in close proximity at the 9p21 locus, encoding cyclin-dependent kinases 4/6 inhibitors of relative molecular mass 16 kD and 15 kD, respectively and also found to be deleted at a high frequency in tumor cell lines. We analyzed p16INK4A and p15INK4B genes in 178 cases of primary leukemias including 81 cases of chronic lymphocytic leukemia (CLL), seven of hairy cell leukemia (HCL), seven of chronic myelogenous leukemia (CML), 43 of acute myelogenous leukemia (AML), 27 of acute lymphoblastic leukemia (ALL), and 13 of myelodysplastic syndrome (MDS) by Southern blot analyses. The ALL cases showed a relatively high frequency of homozygous deletions (22%, 6 of 27) at the p16INK4A gene locus. Interestingly, of the six cases with p16INK4A homozygous deletions, only three showed homozygous deletions at the p15INK4B gene. In 81 CLL patients, we detected one homozygous and five heterozygous deletions at both the p16INK4A and p15INK4B genes and two heterozygous deletions at the p16INK4A gene alone. Deletion of these two genes in AML cases is relatively low (9%). We did not detect deletions in any of the MDS, HCL, and CML cases examined. Sequence analyses of p16INK4A gene of six CLL cases with heterozygous deletion at this locus showed a 27-bp deletion at the splice acceptor site of intron 1 in one case and changes in the coding sequence in three other cases. The data presented in this report showed that (1) p16INK4A and p15INK4B genes are preferentially deleted homozygously in ALL and heterozygously in CLL cases with frequent mutation in the second allele, and (2) p16INK4A gene appears to be more frequently deleted than p15INK4B gene.     

Combinations of Monoclonal Antibodies to Anthrax Toxin Manifest New Properties in Neutralization Assays

Monoclonal antibodies (MAbs) are potential therapeutic agents against Bacillus anthracis toxins, since there is no current treatment to counteract the detrimental effects of toxemia. In hopes of isolating new protective MAbs to the toxin component lethal factor (LF), we used a strain of mice (C57BL/6) that had not been used in previous studies, generating MAbs to LF. Six LF-binding MAbs were obtained, representing 3 IgG isotypes and one IgM. One MAb (20C1) provided protection from lethal toxin (LeTx) in an in vitro mouse macrophage system but did not provide significant protection in vivo. However, the combination of two MAbs to LF (17F1 and 20C1) provided synergistic increases in protection both in vitro and in vivo. In addition, when these MAbs were mixed with MAbs to protective antigen (PA) previously generated in our laboratory, these MAb combinations produced synergistic toxin neutralization in vitro. But when 17F1 was combined with another MAb to LF, 19C9, the combination resulted in enhanced lethal toxicity. While no single MAb to LF provided significant toxin neutralization, LF-immunized mice were completely protected from infection with B. anthracis strain Sterne, which suggested that a polyclonal response is required for effective toxin neutralization. In total, these studies show that while a single MAb against LeTx may not be effective, combinations of multiple MAbs may provide the most effective form of passive immunotherapy, with the caveat that these may demonstrate emergent properties with regard to protective efficacy.     

1324 prison suicides in 10 countries in South America: incidence,relative risks,and ecological factors

Purpose

Although suicide rates of prison populations and incidence factors have been reported for high-income countries, data from low- and middle-income regions are lacking. The purpose of the study was to estimate suicide rates among prison populations in South America, to examine prison-related factors, and to compare suicide rates between prison and general populations.

Methods

In this observational study, we collected the numbers of suicides in prison, rates of prison occupancy, and incarceration rates from primary sources in South America between 2000 and 2017. We compared suicide rates among prisoners with incidence rates in the general populations by calculating incidence rate ratios. We assessed the effect of gender, year, incarceration rates and occupancy on suicide rates in the prison populations using regression analyses.

Results

There were 1324 suicides reported during 4,437,591 person years of imprisonment between 2000 and 2017 in 10 South American countries. The mean suicide rate was 40 (95% CI 16–65) per 100,000 person years for male and female genders combined. The pooled incidence rate ratio of suicide between prison and general populations was 3.9 (95% CI 3.1–5.1) for both genders combined, 2.4 (95% CI 1.9–3.1) for men and a higher ratio in women (13.5, 95% CI 6.9–26.9). High occupancies of prisons were associated with lower incidence of suicide (β = − 58, 95% CI − 108.5 to − 7.1).

Conclusions

Suicides during imprisonment in South America are an important public health problem. Suicide prevention strategies need to target prison populations.