Higher gastric mucin secretion and lower gastric acid output in first-degree relatives of gastric cancer patients

BACKGROUND: Patients infected by Helicobacter pylori who have first-degree relatives with gastric cancer have an 8-fold increased risk of developing gastric cancer themselves. Mucins are high-molecular-weight glycoproteins that play a cardinal role in the protective mechanism of the gastric epithelium. AIM: To study gastric acid and mucin secretion in dyspeptic patients with and without a family history of gastric cancer and H. pylori infection. MATERIALS AND METHODS: Twenty-six dyspeptic patients underwent esophago-gastro-duodenoscopy, gastric biopsies, and acid and mucin secretory tests. The sample was divided by family history of gastric cancer and H. pylori status. RESULTS: Patients who were infected by H. pylori had a significantly higher degree of inflammation than those who were not. H. pylori-positive patients with a positive family history had a lower basal and maximal gastric acid output than infected patients with no family history and noninfected controls, and a higher basal and maximal mucin output than infected patients with no family history. MUC5AC was the major mucin species expressed in gastric juice. CONCLUSIONS: In patients with relatives with gastric cancer, H. pylori infection is associated with a more severe inflammatory reaction consisting of decreased gastric acid secretion and increased mucin secretion.     

Efficacy of Single and Combined Antibiotic Treatments of Anthrax in Rabbits

Respiratory anthrax is a fatal disease in the absence of early treatment with antibiotics. Rabbits are highly susceptible to infection with Bacillus anthracis spores by intranasal instillation, succumbing within 2 to 4 days postinfection. This study aims to test the efficiency of antibiotic therapy to treat systemic anthrax in this relevant animal model. Delaying the initiation of antibiotic administration to more than 24 h postinfection resulted in animals with systemic anthrax in various degrees of bacteremia and toxemia. As the onset of symptoms in humans was reported to start on days 1 to 7 postexposure, delaying the initiation of treatment by 24 to 48 h (time frame for mass distribution of antibiotics) may result in sick populations. We evaluated the efficacy of antibiotic administration as a function of bacteremia levels at the time of treatment initiation. Here we compare the efficacy of treatment with clarithromycin, amoxicillin-clavulanic acid (Augmentin), imipenem, vancomycin, rifampin, and linezolid to the previously reported efficacy of doxycycline and ciprofloxacin. We demonstrate that treatment with amoxicillin-clavulanic acid, imipenem, vancomycin, and linezolid were as effective as doxycycline and ciprofloxacin, curing rabbits exhibiting bacteremia levels of up to 10⁵ CFU/ml. Clarithromycin and rifampin were shown to be effective only as a postexposure prophylactic treatment but failed to treat the systemic (bacteremic) phase of anthrax. Furthermore, we evaluate the contribution of combined treatment of clindamycin and ciprofloxacin, which demonstrated improvement in efficacy compared to ciprofloxacin alone.     

Regulation of sperm capacitation and the acrosome reaction by PIP2 and actin modulation

Actin polymerization and development of hyperactivated (HA) motility are two processes that take place during sperm capacitation. Actin polymerization occurs during capacitation and prior to the acrosome reaction, fast F-actin breakdown takes place. The increase in F-actin during capacitation depends upon inactivation of the actin severing protein, gelsolin, by its binding to phosphatydilinositol-4, 5-bisphosphate (PIP₂) and its phosphorylation on tyrosine-438 by Src. Activation of gelsolin following its release from PIP₂ is known to cause F-actin breakdown and inhibition of sperm motility, which can be restored by adding PIP₂ to the cells. Reduction of PIP₂ synthesis inhibits actin polymerization and motility, while increasing PIP₂ synthesis enhances these activities. Furthermore, sperm demonstrating low motility contained low levels of PIP₂ and F-actin. During capacitation there was an increase in PIP₂ and F-actin levels in the sperm head and a decrease in the tail. In spermatozoa with high motility, gelsolin was mainly localized to the sperm head before capacitation, whereas in low motility sperm, most of the gelsolin was localized to the tail before capacitation and translocated to the head during capacitation. We also showed that phosphorylation of gelsolin on tyrosine-438 depends upon its binding to PIP₂. Stimulation of phospholipase C, by Ca²⁺-ionophore or by activating the epidermal-growth-factor-receptor, inhibits tyrosine phosphorylation of gelsolin and enhances enzyme activity. In conclusion, these data indicate that the increase of PIP₂ and/or F-actin in the head during capacitation enhances gelsolin translocation to the head. As a result, the decrease of gelsolin in the tail allows the maintenance of high levels of F-actin in this structure, which is essential for the development of HA motility.To acquire the ability to fertilize the egg, mammalian spermatozoa must undergo several biochemical and morphological changes in the female reproductive tract, collectively called capacitation. These changes include cAMP/PKA activation, cholesterol efflux from the plasma membrane, PKA-dependent protein tyrosine phosphorylation, actin polymerization and the development of HA motility.1,2 In a recent study we suggested a mechanism by which the Ser/Thr targeting PKA can lead to Tyr phosphorylation of proteins in the capacitation process. We showed that PKA activates Src which, in turn, inhibits the phosphatase PP1, leading to CaMKII activation, which activates Pyk2 to phosphorylate phosphatidyl-inositol-3-kinase on tyr-458.3We have shown elsewhere that actin polymerization must take place in order to capacitate spermatozoa while very fast depolymerization of F-actin occurs prior to the acrosome reaction.4 It has been suggested that an increase in F-actin during capacitation creates a network in the sperm head between the plasma membrane and the outer acrosomal membrane, and the dispersion of this F-actin must occur to enable acrosomal exocytosis.4,5,6,7 The increase in F-actin in the sperm tail during capacitation is important for the development of HA motility.8 The latter is characterized by an increase in flagellar bending amplitude and an increase in average lateral head movement.9,10 It was shown that the efficiency of HA sperm to penetrate the egg is much higher than non-HA sperm.11 Sperm motility and HA motility are mediated by PLD-dependent actin polymerization.8 It is known that phosphatidylinositol 4,5-bisphosphate (PIP₂) is a cofactor for PLD activation in many cell types.12,13,14,15,16 PIP₂ comprises only 1% of plasma membrane phospholipids, however its extraordinary versatility puts it in the center of plasma membrane dynamics governing cell motility, adhesion, endo- and exocytosis.17,18PIP₂ serves as an effector of several proteins such as Myristoylated alanine-rich C-kinase substrate (MARCKS), gelsolin, PLD and PI3K. These proteins are present in spermatozoa19,20 and are involved in the regulation of sperm capacitation and/or the acrosome reaction. PIP₂ binds gelsolin and release it from actin filaments ends, exposing sites for actin assembly.21 We have shown that the release of bound gelsolin from PIP₂, causes rapid Ca²⁺-dependent F-actin depolymerization as well as an increased acrosome reaction.22 We have also shown that PIP₂ and gelsolin are involved in regulating sperm motility and the development of HA motility.23     

Diagnosis and treatment of urinary tract complications in Crohn's disease: an experience over 15 years.

BACKGROUND: Urinary tract complications in Crohn's disease are common but treatable, and often present diagnostic and therapeutic dilemmas. PURPOSE: To determine the incidence of urinary tract complications in patients with Crohn's disease in Israel and to report an experience over 15 years of patients with Crohn's disease, with the aim of illustrating the diverse patterns of presentation, and thereby broadening the approach to diagnosis and treatment. METHODOLOGY: Clinical and radiological findings of 312 patients with Crohn's disease were reviewed. RESULTS: Simple cystitis was the most common problem, occurring in 51 patients. The problem seldom required hospitalization and was instead managed in the ambulatory setting. A review revealed that 22 patients with urinary tract complications required hospitalization. Six patients had ileovesical fistulas. In one patient, the colon was also affected. In another patient, radiological and endoscopic studies failed to identify the fistula, which was confirmed during surgery. All six patients were treated surgically. Four patients had ureteral obstructions and hydronephrosis, three of whom responded well to conservative treatment. In one patient, the affected ileal segment was resected. Four patients suffered from retroperitoneal abscess accompanied by urinary symptoms. Twelve patients developed right kidney stones. All of the patients suffered from long-standing Crohn's disease with bowel resection. Surprisingly, most of the severe complications occurred in men, although 70% of the patients were women. CONCLUSIONS: Based on these findings, urological complications are not rare in patients with Crohn's disease, and necessitate a high degree of diligence and periodic urological evaluation.     

Ultrasonically Guided Fine-Needle Aspiration of Liver Lesions

The aim of the present study was to determine the diagnostic accuracy of ultrasonically guided fine-needle aspiration for liver lesions detected by ultrasound scan. A total of 142 aspirations were carried out in 129 patients with unifocal or multifocal liver lesions suspected of malignancy. The aspiration was made with a 22-gauge needle, guided by ultrasound. Based on histological, cytological, and clinical findings, final diagnoses were reached in 123 patients, 96 of whom had malignant liver disease and 27 benign liver disease. Among the 96 patients with malignant liver disease, the cytological findings revealed malignancy in 78 patients (81.3%) and suspected malignancy in five patients (5.1%), but failed to demonstrate malignancy in 13 patients (13.3%). Among 27 patients with benign liver disease, all the cytological findings indicated benignancy. The overall sensitivity, specificity, and positive and negative predictive values for cytological findings were 86.5%, 100%, 100%, and 76.9%, respectively. The diagnostic accuracy of ultrasonically guided fine-needle aspiration was 89.4%. In one patient with incipient chronic disseminated intravascular coagulation, a fatal intraperitoneal bleeding complicated the procedure. We conclude that ultrasonically guided FNA for cytologic diagnosis of liver lesions is highly accurate and is only rarely associated with fatal complication.     

Aggression–impulsivity,mental pain,and communication difficulties in medically serious and medically non-serious suicide attempters

Background

Unbearable mental pain, depression, and hopelessness have been associated with suicidal behavior in general, while difficulties with social communication and loneliness have been associated with highly lethal suicide attempts in particular. The literature also links aggression and impulsivity with suicidal behavior but raises questions about their influence on the lethality and outcome of the suicide attempt.

Objectives

To evaluate the relative effects of aggression and impulsivity on the lethality of suicide attempts we hypothesized that impulsivity and aggression differentiate between suicide attempters and non-attempters and between medically serious and medically non-serious suicide attempters.

Method

The study group included 196 participants divided into four groups: 43 medically serious suicide attempters; 49 medically non-serious suicide attempters, 47 psychiatric patients who had never attempted suicide; and 57 healthy control subjects. Data on sociodemographic parameters, clinical history, and details of the suicide attempts were collected. Participants completed a battery of instruments for assessment of aggression–impulsivity, mental pain, and communication difficulties.

Results

The medically serious and medically non-serious suicide attempters scored significantly higher than both control groups on mental pain, depression, and hopelessness (p < .001 for all) and on anger-in, anger-out, violence, and impulsivity (p < .05 for all), with no significant difference between the two suicide attempter groups. Medically serious suicide attempters had significantly lower self-disclosure (p < .05) and more schizoid tendencies (p < .001) than the other three groups and significantly more feelings of loneliness than the medically non-serious suicide attempters and nonsuicidal psychiatric patients (p < .05). Analysis of aggression–impulsivity, mental pain, and communication variables with suicide lethality yielded significant correlations for self-disclosure, schizoid tendency, and loneliness. The interaction between mental pain and schizoid traits explained some of the variance in suicide lethality, over and above the contribution of each component alone.

Conclusions

Aggression–impulsivity and mental pain are risk factors for suicide attempts. However, only difficulties in communication differentiate medically serious from medically non-serious suicide attempters. The combination of unbearable mental pain and difficulties in communication has a magnifying effect on the risk of lethal suicidal behavior.