Melatonin reduces phosphine-induced lipid and DNA oxidation in vitro and in vivo in rat brain

Phosphine (PH(3)), a widely used pesticide, was found in our recent study to induce oxidative damage in the brain, liver and lung of rats. We also observed that melatonin significantly blocked this action. The present study focused on brain and the magnitude and mechanism of protection of PH(3)-induced oxidative damage by melatonin in vitro and in vivo. PH(3) in whole brain homogenate (3 mg protein/mL Tris-HCl pH 7.4 buffer) induced increasing lipid peroxidation [as malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA)] dependent on concentration (0.25-2 mM) and time (30-150 min), reaching a maximum level of 2.9-fold at 90 min after PH(3) at 1 mM. Elevation of MDA + 4-HDA levels by PH(3) at 1 mM was also observed in homogenates of cerebral cortex, cerebellum, hippocampus and hypothalamus examined individually. Melatonin at 0.1-2 mM progressively inhibited PH(3)-induced lipid peroxidation in brain and regions thereof. Additionally, PH(3) induced brain DNA oxidation in vitro and in vivo determined as 8-hydroxyguanosine (8-OH-dG). Melatonin at 1 mM significantly suppressed PH(3)-induced brain DNA oxidation in vitro. PH(3) at 4 mg/kg i.p. significantly elevated 8-OH-dG in frontal cortex and melatonin prevented it. PH(3) in vivo marginally lowered brain glutathione peroxidase activity and melatonin restored it completely. In contrast, PH(3) and melatonin both stimulated superoxide dismutase production. Brain glutathione (GSH) levels in PH(3)-treated rats were significantly reduced at 30 min and recovered gradually. It is concluded that melatonin, probably because of its free radical scavenging ability, confers marked protection against PH(3)-induced oxidative toxicity in brain.     

Recognition and management of overweight and obesity in primary care in Germany

BACKGROUND: In contrast to the well-documented high prevalence of overweight and obesity in the general population, the prevalence, recognition rates and management by primary care physicians--as the core gatekeeper in the health care system--remains poorly studied. PURPOSE OF THE STUDY: To examine (1) the point prevalence of overweight (BMI 25.0-29.9 kg/m(2)) and obesity (BMI> or =30 kg/m(2)) in primary care patients, (2) prevalence patterns in patients with high-risk constellations (diabetes, hypertension, cardiovascular disease, etc.), (3) doctors' recognition and interventions, as well as patients' use and perceived effectiveness of weight-loss interventions and (4) factors associated with non-treatment. METHODS: Cross-sectional point prevalence study of 45 125 unselected consecutive primary care attendees recruited from a representative nationwide sample of 1912 primary care practices. Measures: (1) standardized clinical appraisal of each patient by the physician (diagnostic status and recognition, severity, comorbidity, current and past interventions). (2) Patient self-report questionnaire: height and weight, illness history, past and current treatments and their perceived effectiveness, health attitudes and behaviors. RESULTS: (1) In all, 37.9% of all primary care attendees were overweight, 19.4% obese. (2) Rates for overweight and obesity were highest in patients with diabetes (43.6 and 36.7%) and hypertension (46.1 and 31.3%), followed by patients with cardiovascular disorders. Rates of overweight/obesity increased steadily by the number of comorbid conditions. (3) Doctors' recognition of overweight (20-30%) and obesity (50-65%) was low, patients' actual use of weight control interventions even lower (past 12 months: 8-11%, lifetime: 32-39%). Patient success rates were quite limited. (4) Co- and multimorbidity in particular as well as other patient and illness variables were identified as predictors for recognition, but prediction of patients' actual use of weight loss interventions was limited. CONCLUSIONS: Primary care management of overweight and obesity is largely deficient, predominantly due to four interrelated factors: doctors' poor recognition of patients' weight status, doctors' inefficient efforts at intervention, patients' poor acceptance of such interventions and dissatisfaction with existing life-style modification strategies.     

Differences in constitutive and post-methotrexate folylpolyglutamate synthetase activity in B-lineage and T-lineage leukemia

Folylpolyglutamate synthetase (FPGS) is responsible for the metabolism of natural folates and a broad range of folate antagonists to polyglutamate derivatives. Recent studies indicated increased accumulation of methotrexate (MTX) polyglutamates (MTX-PG) in blast cells as a predictor of favorable treatment outcome in childhood acute lymphoblastic leukemia (ALL). We determined the expression of FPGS activity in blasts from children with ALL at diagnosis and after treatment with MTX as a single agent, before conventional remission induction therapy. The levels of enzyme activity in ALL blasts at diagnosis (median of 689 pmol/h/mg protein) were significantly higher (P = .003) than those found in acute nonlymphoblastic leukemia (ANLL) blasts (median of 181 pmol/h/mg protein). Comparable lineage differences in normal lymphoid versus nonlymphoid cells suggest a lineage-specific control of FPGS expression, FPGS activity increased in ALL blasts after in vivo exposure to MTX. The median increase in FPGS activity was significantly higher (P = .003) in B-lineage ALL (188%) than in T-lineage ALL (37%). Likewise, the percentage of intracellular long chain MTX-PG (Glu3-6) was significantly higher (P = .02) in B- lineage ALL (92%) than in T-lineage ALL (65%), consistent with higher FPGS activity in B-lineage blasts. This finding could explain, at least in part, the superior outcome in children with B-lineage ALL treated with antimetabolite therapy.     

The heart in dermatomyositis and polymyositis

We studied eleven consecutive patients: eight with Dermatomyositis (DM) and three with Polymyositis (PM) from the cardiological point of view through non invasive methods. Nine patients (82%) had some kind of cardiopulmonary complications as shown by any of the used methods. Symptoms: eight (73%) referred some kind of cardiopulmonary symptoms, mainly dyspnea; Physical examination; in seven (64%) was abnormal, detecting increased second pulmonary sound in four (36%), findings of mitral valve prolapse (MVP) in two (18%) and in two (18%) S3 gallop; Electrocardiogram: in seven (64%) was abnormal; six (55%) had some kind of heart enlargement corresponding four (36%) to right atrial or ventricular hypertrophy (RAH & RVH) and two (18%) to left ventricular hypertrophy (LVH), three (27%) had incomplete or complete right bundle branch block, one (9%) had bifascicular block and one (9%) left anterior hemiblock. Two (18%) had sinus tachycardia and two (18%) atrial premature contractions; d) chest ray: six (55%) were abnormal, among them, three (27%) had pulmonary fibrosis, three (27%) had RAH and/or RVH, two (18%) had LVH and one (9%) pericardial effusion; e) Echocardiogram: was abnormal in eight (73%), corresponding three (27%) to RVH, three to MVP which has been considered rare, in two (18%) congestive cardiomyopathy, in two (18%) pericardial effusion and in one (9%) type "A" paradoxical septal movement.     

Insulin binding and action in adipocytes in vitro in relation to insulin action in vivo in young and middle-aged subjects

The effect of age on glucose metabolism in vivo was compared to that found in adipocytes in vitro in young (n = 8, age 23 to 31 years) and middle-aged (n = 7, age 37 to 55 years) non-diabetic subjects. During the OGTT, the incremental glucose or insulin areas did not differ significantly between the groups. Fasting and 2 h plasma glucose (P less than 0.01) and the 2 h plasma insulin (P less than 0.05) levels were, however, slightly higher in the middle-aged than in the young group. During iv induced hyperinsulinaemia (approximately 85 mU/l), rates of glucose uptake were comparable between the middle-aged (6.32 +/- 0.94 mg/kg/min) and the young subjects (7.56 +/- 0.78 mg/kg/min, P greater than 0.5). In fat cells, both basal and insulin stimulated rates of glucose transport were 35% lower (P less than 0.05) in the middle-aged than in the young subjects. Basal and insulin stimulated rates of glucose oxidation and lipogenesis were both markedly lower (P less than 0.01) in the middle-aged than in the young group. The rates of glucose transport, oxidation and lipogenesis were inversely related to age, whereas none of these parameters was related to fat cell size. In conclusion, adipocyte glucose metabolism in middle-aged healthy subjects was markedly impaired. In contrast, rates of glucose uptake during iv hyperinsulinaemia and glucose responses during hyperinsulinaemia in the OGTT were comparable in young and middle-aged subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms for racial and ethnic disparities in glycemic control in middle-aged and older Americans in the health and retirement study

BACKGROUND: Mechanisms for racial/ethnic disparities in glycemic control are poorly understood. METHODS: A nationally representative sample of 1901 respondents 55 years or older with diabetes mellitus completed a mailed survey in 2003; 1233 respondents completed valid at-home hemoglobin A(1c) (HbA(1c)) kits. We constructed multivariate regression models with survey weights to examine racial/ethnic differences in HbA(1c) control and to explore the association of HbA(1c) level with sociodemographic and clinical factors, access to and quality of diabetes health care, and self-management behaviors and attitudes. RESULTS: There were no significant racial/ethnic differences in HbA(1c) levels in respondents not taking antihyperglycemic medications. In 1034 respondents taking medications, the mean HbA(1c) value (expressed as percentage of total hemoglobin) was 8.07% in black respondents and 8.14% in Latino respondents compared with 7.22% in white respondents (P < .001). Black respondents had worse medication adherence than white respondents, and Latino respondents had more diabetes-specific emotional distress (P < .001). Adjusting for hypothesized mechanisms accounted for 14.0% of the higher HbA(1c) levels in black respondents and 19.0% in Latinos, with the full model explaining 22.0% of the variance. Besides black and Latino ethnicity, only insulin use (P < .001), age younger than 65 years (P = .007), longer diabetes duration (P = .004), and lower self-reported medication adherence (P = .04) were independently associated with higher HbA(1c) levels. CONCLUSIONS: Latino and African American respondents had worse glycemic control than white respondents. Socioeconomic, clinical, health care, and self-management measures explained approximately a fifth of the HbA(1c) differences. One potentially modifiable factor for which there were racial disparities--medication adherence--was among the most significant independent predictors of glycemic control.     

Interconversion of cortisol and cortisone in baboon trophoblast and decidua cells in culture

In baboons, transplacental cortisol (F)/cortisone (E) metabolism changes from reduction (E to F) at midgestation to oxidation (F to E) near term when estrogen becomes elevated. Indeed, estrogen regulates the placental microsomal 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) enzyme catalyzing F oxidation. However, regulation of 11 beta-HSD-reductase (E to F) is unknown, because this enzyme is destroyed by microsomal isolation. Therefore, we used cell culture to determine the role of estrogen on placental reduction of E to F and to ascertain whether estrogen regulation of the oxidation of F to E was specific to trophoblast. Placentas were obtained on day 165 (n = 6; term, day 184) and on day 100 of gestation from baboons untreated (n = 8) or treated (n = 6) with 50-mg implants of androstenedione (delta 4A) inserted sc in the mother between days 70 and 100 of gestation to increase placental estrogen production. After removal of fetal membranes, the decidua basalis and trophoblast were separated, rinsed repeatedly in medium-199, minced, and then incubated in trypsin/DNase. Dispersed cells were layered onto a discontinuous Percoll gradient (5-70%), and purified cytotrophoblast (TC; 1.048-1.062 g/ml) and decidua (DC; 1.048-1.062 g/ml) were harvested. After incubation in media containing 10% fetal bovine serum to permit attachment, cells were incubated (24 h) in Dulbecco's modified Eagle's medium containing 10,100, or 500 ng [3H]F or [3H]E. F and E in medium were purified by HPLC and the interconversion of F/E calculated. Equilibrium was achieved by 12 h, and F/E metabolism was proportional to cell number and substrate (10-500 ng) concentration. At substrate concentrations of 500 ng/ml, the reduction of E to F (range, 81-195 ng F produced/24 h) in the DC (0.5 x 10(6) cells) was greater (P less than 0.05) than oxidation of F to E (19-28 ng E/24 h) in all groups. This pattern of metabolism by DC was not affected by time of gestation or treatment with delta 4A. In the TC (2.5 x 10(6) cells), oxidation of F to E always exceeded (P less than 0.05) reduction of E to F. Moreover, the conversion of F to E by TC of day 100 (86 +/- 26 ng E/24 h; mean +/- SE) was increased (P less than 0.05) by delta 4A (195 +/- 35) and greater (P less than 0.05) at day 165 (213 +/- 40). In contrast, TC metabolism of E (21-57 ng F/24 h) was similar in all groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and BAL in COPD

BACKGROUND: The single-breath N(2) test (sbN(2)-test) is closely related to small airways pathology in resected lung specimens of smokers. We investigated whether uneven ventilation and airway closure are associated with specific markers of airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in patients with manifest COPD. METHODS: Fifty-one patients with stable COPD not receiving corticosteroids were examined in a cross-sectional study (43 men; mean [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41 [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry (FEV(1), 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [DeltaN(2)], closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL (only in the first half of patients), and induced sputum. Neutrophil elastase (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels were determined in BAL fluid. RESULTS: DeltaN(2) increased with subepithelial neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated with any other inflammatory cell type in BAL or biopsies, nor with inflammatory cell counts in sputum. Of importance, the correlations between DeltaN(2) and BAL NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained significant when adjusting for FEV(1) percentage of predicted. CONCLUSIONS: The results of the sbN(2)-test are associated with neutrophilic inflammation in bronchial biopsies and BAL in patients with COPD. Our findings support a role of neutrophilic inflammation in the pathogenesis of small airways dysfunction in COPD.     

Adaptations in capillarization and citrate synthase activity in response to endurance training in older and young men

The time-course of adaptation in cardiorespiratory fitness, measures of capillarization, and citrate synthase (CS) activity were examined in seven older (O; 69 ± 7 years) and seven young (Y; 22 ± 1 years) men pre-, mid-, and posttraining during a 12-week endurance training program. Training was performed on a cycle ergometer three times per week for 45 minutes at ~70% of maximal VO(2) (VO(2max)). VO(2max) and maximal cardiac output increased similarly from pre- to posttraining in O and Y (p < .05), and maximal a-vO(2diff) was greater (p < .05) posttraining in O and Y. CS was elevated at mid- and posttraining compared with pretraining in both O and Y (p < .05). Indices of capillarization increased 30%-40% in O and 20%-30% in Y and were elevated at posttraining compared with pre- and midtraining in both groups (p < .05). This study showed that both O and Y undertaking similar endurance training displayed capillary angiogenesis and improved mitochondrial respiratory capacity.     

上海地区中国人血脂紊乱类型与胰岛素抵抗

目的：探讨上海地区中国人脂代谢紊乱的类型与胰岛素抵抗的关系。方法：830例年龄≥40岁（男300例,女530例）正常人和血脂紊乱者,后者分为7个亚组,包括单纯低高密度脂蛋白（HDL）组（亚组Ⅰ）、单纯高甘油三酯（TG）组（亚组Ⅱ）、单纯高胆固醇（TC）或高低密度脂蛋白（LDL）组（亚组Ⅲ）、低HDL合并高TG组（亚组Ⅳ）、低HDL合并高TC或高LDL组（亚组Ⅴ）、高TG合并高TC或高LDL组（亚组Ⅵ）、低HDL合并高TG及高TC或高LDL组（亚组Ⅶ）,用稳态模式评估法（HOMA）评价胰岛素抵抗（IR）。结果：校正年龄、性别、体重指数等因素后,伴有高TG的各血脂异常 亚组的胰岛素抵抗指数升高较为明显,总体脂、腹部脂肪对血脂紊乱的影响较为显著;体脂对胰岛素抵抗指数的影响部分是通过TG介导的,结论：TG升高可作为个体存在胰岛纱抵抗的指标。     

Glycosuria and diabetes mellitus in children and adolescents in south India.

In Madras city (India) 10,513 school students between 3 and 20 yr of age were investigated for glycosuria and its causes. While no previously known cases of diabetes mellitus of any type were encountered, four students (0.038%) in the survey population were found to have glycosuria. One (0.009%) had renal glycosuria, two (0.019%) were possibly NIDDY (MODY) and one (0.009%) had transient glycosuria while receiving anti-tuberculous chemotherapy. It is therefore concluded that neither diabetes mellitus nor glycosuria of non-diabetic causes is a crucial health problem in Indian children and adolescents. While the reasons for this are not known, further research in this field could be of global interest.     

Estradiol and progesterone receptors in normal and pathologic colonic mucosa in humans

The presence of estradiol (E) and progesterone (Pg) receptors (R) has been demonstrated also in normal and neoplastic tissues known to be hormone-independent and in particular in primitive colonic cancer, and, possibly, in healthy colonic mucosa. In this study endoscopic and surgical colonic mucosa specimens from 55 subjects were analyzed and divided as follows: 21 samples from healthy subjects, 12 normal mucosa samples from subjects affected with colonic cancer, 8 adenomatous polyps specimens, 5 samples from ulcerative colitis drawn on areas showing macroscopic lesions and 9 colonic cancer specimens. In the control group we have observed 6 cases positive for ER (28.6%) and 2 positive for PgR (14.3%). Six normal mucosa specimens from subjects affected with colonic cancer were found to be positive for ER (50%) and 2 for PgR (16.7%). Five colonic cancers resulted ER positive (55.5%) and 4 PgR positive (44.4%). Four polyps were ER positive (50%) and 3 PgR positive (37.5%); in this group only one subject showed positive binding in the surrounding normal tissue. These data confirm the presence of ER and PgR in colonic cancer and colonic adenomas (so-called precancerous disease); in these subjects the finding of steroid receptors also in normal mucosa suggests that the presence of steroid binding could be considered as a marker of a precancerous condition.     

Hemoglobin Switching in Sheep and Goats: Change in Functional Globin Messenger RNA in Reticulocytes and Bone Marrow Cells

ANEMIA CAUSES A CHANGE IN THE TYPE OF CIRCULATING HEMOGLOBIN IN GOATS AND CERTAIN SHEEP: HbA (alpha(2)beta(2) (A)) is replaced by HbC (alpha(2)beta(2) (C)). We have isolated globin mRNA from erythroid cells of anemic and nonanemic animals to investigate the mechanism whereby anemia causes this switch. To study several stages in transition from beta(A) to beta(C) synthesis, active globin mRNA was isolated from bone marrow cells, as well as from reticulocytes. By assaying these globin mRNAs in a rabbit reticulocyte cell-free system, we have demonstrated that the switch from beta(A) to beta(C) globin synthesis is mediated via a change in functional globin mRNA.     

Differentiation pathways in carcinogenesis and in chemo- and radioresistance

Cancer stem cells (CSCs) share many features with embryonic stem cells (ESCs) such as the ability for self-renewal and differentiation. Signaling pathways that are involved in these processes are also involved in chemo- and radioresistance (e.g. Wnt, Notch and Hedgehog pathways). This review is focused on the influence of three important differentiation pathways on carcinogenesis and on chemo- and radioresistance in ESCs and CSCs.     

Clinically relevant progestins regulate neurogenic and neuroprotective responses in vitro and in vivo

Previously, we demonstrated that progesterone (P(4)) promoted adult rat neural progenitor cell (rNPC) proliferation with concomitant regulation of cell-cycle gene expression via the P(4) receptor membrane component/ERK pathway. Here, we report the efficacy of seven clinically relevant progestins alone or in combination with 17β-estradiol (E(2)) on adult rNPC proliferation and hippocampal cell viability in vitro and in vivo. In vitro analyses indicated that P(4), norgestimate, Nestorone, norethynodrel, norethindrone, and levonorgestrel (LNG) significantly increased in rNPC proliferation, whereas norethindrone acetate was without effect, and medroxyprogesterone acetate (MPA) inhibited rNPC proliferation. Proliferative progestins in vitro were also neuroprotective. Acute in vivo exposure to P(4) and Nestorone significantly increased proliferating cell nuclear antigen and cell division cycle 2 expression and total number of hippocampal 5-bromo-2-deoxyuridine (BrdU)-positive cells, whereas LNG and MPA were without effect. Mechanistically, neurogenic progestins required activation of MAPK to promote proliferation. P(4), Nestorone, and LNG significantly increased ATP synthase subunit α (complex V, subunit α) expression, whereas MPA was without effect. In combination with E(2), P(4), Nestorone, LNG, and MPA significantly increased BrdU incorporation. However, BrdU incorporation induced by E(2) plus LNG or MPA was paralleled by a significant increase in apoptosis. A rise in Bax/Bcl-2 ratio paralleled apoptosis induced by LNG and MPA. With the exception of P(4), clinical progestins antagonized E(2)-induced rise in complex V, subunit α. These preclinical translational findings indicate that the neurogenic response to clinical progestins varies dramatically. Progestin impact on the regenerative capacity of the brain has clinical implications for contraceptive and hormone therapy formulations prescribed for pre- and postmenopausal women.     

Estrogenic activity in vivo and in vitro of some diethylstilbestrol metabolites and analogs

The diethylstilbestrol (DES) metabolite (beta-dienestrol), which had been identified in mouse, rat, monkey, and human urine, and two proposed metabolic intermediates (diethylstilbestrol alpha,alpha'-epoxide and alpha,alpha'-dihydroxy DES) were synthesized and their estrogenic activities determined. In addition, three DES analogs, alpha-dienestrol, DES-dihydroxy diethyl phenanthrene (DES-phenanthrene), and 1-(alpha-ethyl, 4alpha-hydroxyphenyl)indanyl-5-ol (indanyl-DES), were studied. Estrogenic activities of the compounds in vivo were determined by the immature mouse uterine weight bioassay; in vitro, their estradiol receptor binding activity (competitive equilibrium binding, sucrose gradient analysis, and association rate inhibition assays) was determined. Results of the mouse uterine weight bioassay gave the following order of estrogenicity: DES > alpha-dienestrol >/= DES-epoxide > indanyl-DES > dihydroxy DES > beta-dienestrol > DES-phenanthrene. Results of competitive equilibrium binding analyses of these compounds with estradiol-17beta for the mouse uterine cytosol receptor followed the same order seen for the bioassay, except for indanyl-DES. DES, indanyl-DES, and alpha-dienestrol had the greatest affinities (K(a) values approximately 0.5-19.1 x 10(10) M(-1)), while DES-phenanthrene had the lowest (K(a) = 3.5 x 10(7) M(-1) +/- 1.2). Sucrose gradient analysis of the above competition preparations illustrated the displacement of [(3)H]estradiol from the receptor peak. This displacement was receptor specific and concentration dependent and correlated with the equilibrium binding concentrations. In addition, the most hormonally active substances demonstrated the greatest rate inhibition in the estradiol cytosol receptor association rate reaction (V(0)). The rank order of estrogenicity of the compounds determined in this study should be useful in evaluating alternative metabolic pathways of DES as well as distinguishing biologically active metabolites from relatively inactive ones.     

Magnesium and potassium content in patients with heart failure and in healthy persons. Determination in lymphocytes, erythrocytes and plasma

Therapy with diuretics and/or digitalis, as well as the compromised cardiac function, contributes to electrolyte alterations (magnesium, potassium) in patients with congestive heart failure. We determined in 29 patients with heart failure (NYHA classes II-IV) the magnesium and potassium content in lymphocytes and in erythrocytes, as well as in 25 healthy subjects. In patients with heart failure, lymphocyte magnesium (4.4 +/- 0.6 fmol/cell) and lymphocyte potassium (50.4 +/- 6.0 fmol/cell) were only slightly (n.s.) lower compared to controls (Mg++: 4.7 +/- 0.6 fmol/cell; K+: 54.6 +/- 6.8 fmol/cell). Only in healthy subjects did we find a positive correlation between magnesium and potassium in lymphocytes (r = 0.83). The electrolyte content in erythrocytes was also not different in patients with heart failure (Mg++: 2.2 +/- 0.1 mmol/l; K+: 96.6 +/- 6.1 mmol/l) and controls (Mg++: 2.2 +/- 0.1 mmol/l; K+: 97.8 +/- 4.0 mmol/l). There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for lymphocytes, or for erythrocytes in both groups. It is concluded that 1) determinations of magnesium and potassium in plasma do not reflect intracellular electrolyte content; 2) the magnesium and potassium content of lymphocytes and erythrocytes were not different in patients suffering from heart failure compared to controls; and 3) in heart failure, the relationship of magnesium and potassium in lymphocytes may be altered.     

Anti-CagA and anti-VacA antibodies in Helicobacter pylori-infected patients with and without peptic ulcer disease in Serbia and Montenegro

BACKGROUND: The expression of two Helicobacter pylori proteins, CagA and VacA, is associated with more severe pathogenesis and clinical outcomes of the infection. However, this association varies among geographical regions and ethnic groups. We therefore evaluated CagA and VacA seroprevalence in H. pylori-positive dyspeptic patients in Serbia and Montenegro. METHODS: In 173 consecutive dyspeptic patients referred to endoscopy (67M, mean age 49 +/- 15, 76 smokers), immunoblot assay was used to detect serum antibodies against CagA and VacA. Presence of H. pylori infection was assessed using a rapid urease test (RUT), routine histology and serology (anti-IgG ELISA). Duodenal ulcer (DU) was diagnosed in 28, gastric ulcer (GU) in 3 and non-ulcer dyspepsia (NUD) in the remaining 142 patients. RESULTS: 129 (74.6%) patients were H. pylori-positive, 27 (96.4%) with DU, 3 (100%) with GU and 99 (69.7%) with NUD (P < 0.01); 121 (93.8%) patients carried anti-CagA antibodies and there was no difference between the DU and NUD groups. VacA antibodies were detected in sera of 50 (38.75%) and were more prevalent in patients with DU compared to the NUD group (P < 0.05). CONCLUSIONS: In Serbia and Montenegro there is high seroprevalence of CagA-positive H. pylori strains in dyspeptic patients with and without peptic ulcer, while VacA-positive strains are more closely related to peptic ulcer disease.     

Ovulation induction and in vitro fertilization in systemic lupus erythematosus and antiphospholipid syndrome

OBJECTIVE: During ovulation induction (OI), ovarian stimulation is accomplished by hormonal manipulation, which includes administration of gonadotropins, gonadotropin-releasing hormone agonists, follicle-stimulating hormone, and luteinizing hormone. In in vitro fertilization (IVF), progesterone is often added. Because of the possibility of hormone-associated flare or thrombosis, patients with systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (primary APS) undergoing OI/IVF are potentially at increased risk. The present study was conducted in order to assess this risk. METHODS: Nineteen women who underwent 68 cycles of OI/IVF were studied by interview and retrospective chart review. RESULTS: Four OI/IVF cycles (25%) in SLE patients resulted in increased lupus activity and 2 (13%) in ovarian hyperstimulation syndrome. One patient with primary APS who was given heparin during multiple cycles developed osteopenia. No thrombosis occurred. Pregnancy complications included toxemia, lupus flare, gastrointestinal hemorrhage due to Mallory-Weiss tear, polygestation, and diabetes. Postpartum complications included nephritis flare, costochondritis, and suicidal depression. Lupus flares occurred at expected rates. Five of 16 cycles (31%) in 7 SLE patients, 5 of 48 cycles (10%) in 10 primary APS patients, and 0 of 5 cycles in 2 women with antiphospholipid antibody (without SLE or primary APS) resulted in liveborn children, including multiple gestations (3 twin sets with 4 surviving infants and 2 triplet sets with 3 surviving infants). Seven of 14 living children (50%) were premature, 3 had neonatal lupus, and 1 had pulmonic stenosis. Five surviving infants (38%) had complications unrelated to prematurity. CONCLUSION: Although OI/IVF can be successful in SLE and primary APS patients, rates of fetal and maternal complications are high.     

Incidence and Prevalence of Type 1 Diabetes in Children and Adolescents in Benghazi,Libya

The mean annual incidence rates of Type 1 diabetes mellitus in Arab children and adolescents in Benghazi, Libya were assessed as based on prospective registration of patients during the period 1981–1990. Results showed an annual incidence (per 100 000) of 7.0 (6.0–8.2) (males 6.3(5.0–7.9) females 7.8(6.3–9.7)) in 0–14 year olds and 8.8(7.8–10.0) (males 8.3(6.9–10.0), females 9.2(7.7–11.0)) in 0–19 year olds. There were no significant differences between males and females or between season of onset. The commonest age of onset was 15–19 years. Annual variations were significant in the 0–14 years age group (p < 0.001) and non-significant in the 0–19 years age group. In 1981 the age adjusted prevalence rates of Type 1 patients (per 100 000) were 23.5 (17.1–31.5) (males 21.2(13.1–32.3), females 25.9(16.8–38.3)) in 0–14 year olds and 36.2(29.1–45.1) (males 31.4(22.2–43.2), females 41.0(30.2–54.5)) in 0–19 year olds. In 1990 the prevalence rates had increased to 37.3(30.5–45.5) (males 40.7(30.8–53.3), females 33.8 (24.6–45.3)) in 0–14 year olds and 59.5(51.6–58.5) (males 60.3(49.3–73.6), females 58.6 (47.7–72.1)) in 0–19 year olds. Increase in prevalence rates was significant in both sexes and in both age groups (p < 0.001). Increase in prevalence rates in girls in 1981 and in boys in 1990 were not significant. It is concluded that Type 1 diabetes is a common chronic disease of children and adolescents in Benghazi, Libya.