Experimental gastritis in mice enhances anxiety in a gender-related manner

There is a gender-related comorbidity of pain-related and inflammatory bowel diseases with psychiatric diseases. Since the impact of experimental gastrointestinal inflammation on the emotional-affective behavior is little known, we examined whether experimental gastritis modifies anxiety, stress coping and circulating corticosterone in male and female Him:OF1 mice. Gastritis was induced by adding iodoacetamide (0.1%) to the drinking water for at least 7 days. Inflammation was assessed by gastric histology and myeloperoxidase activity, circulating corticosterone determined by enzyme immunoassay, anxiety-related behavior evaluated with the elevated plus maze and stress-induced hyperthermia tests, and depression-like behavior estimated with the tail suspension test. Iodoacetamide-induced gastritis was associated with gastric mucosal surface damage and an increase in gastric myeloperoxidase activity, this increase being significantly larger in female mice than in male mice. The rectal temperature of male mice treated with iodoacetamide was enhanced, whereas that of female mice was diminished. The circulating levels of corticosterone were reduced by 65% in female mice treated with iodoacetamide but did not significantly change in male mice. On the behavioral level, iodoacetamide treatment caused a decrease in nocturnal home-cage activity, drinking and feeding. While depression-related behavior remained unaltered following induction of gastritis, behavioral indices of anxiety were significantly enhanced in female but not male mice. There was no correlation between the estrous cycle and anxiety as well as circulating corticosterone. Radiotracer experiments revealed that iodoacetamide did not readily enter the brain, the blood-brain ratio being 20:1. Collectively, these data show that iodoacetamide treatment causes gastritis in a gender-related manner, its severity being significantly greater in female than in male mice. The induction of gastritis in female mice is associated with a reduction of circulating corticosterone and an enforcement of behavioral indices of anxiety. Gastric inflammation thus has a distinct gender-dependent influence on emotional-affective behavior and its neuroendocrine control.     

Prevalence and characteristics of postpartum thyroid dysfunction in Tehran

OBJECTIVE: To determine the prevalence of postpartum thyroiditis (PPT), one of the autoimmune disorders of the thyroid which usually occurs in women in the first year after parturition. PPT presents with periods of transient thyrotoxicosis and hypothyroidism, in many cases resulting in permanent hypothyroidism. DESIGN: The study involved 1040 mothers who had contacted five health centers in Tehran for vaccination of their children. METHODS: Signs and symptoms of hypothyroidism and thyrotoxicosis, and the presence of goiter (using the World Health Organization classification), were sought. Serum T3, T4, TSH, anti-TPO and anti-Tg antibodies were measured at 3, 4.5, 6 and 9 months after parturition. In those with hypothyroidism or thyrotoxicosis and a matched group of normal women, thyroid sonography was performed. RESULTS: The prevalence of thyroiditis was 11.4%. Hypothyroidism and thyrotoxicosis occurred in 68 and 42 mothers respectively. Nine had thyrotoxicosis followed by hypothyroidism. There was one case of Graves' disease. Out of 68 hypothyroid patients, 33 women underwent treatment with levothyroxine (because of the severity of symptoms) for 12 months. Six women showed increased TSH at 6 weeks after discontinuation of thyroxine. Stage II goiter (World Health Organization classification) were observed in 21.8% of patients and in 6.7% of pospartum euthyroid women (P<0.001). Positive anti-TPO was found in 61.5% of patients and in 19% of the control group; positive anti-Tg was found in 58% of patients and in 6% of the control group (P<0.001). Sonographic changes were observed in 96% of the patients and in 7% of the control group (P<0.001). There was no significant correlation between the occurrence of thyroiditis and parity, the age of the mother, a previous history of thyroid disease in the patient or family, breast-feeding, or the gender of the child. CONCLUSION: The results of this study show a high prevalence of PPT in Tehranian women. This may be due to the length and frequency of follow-up and/or the transition from low to adequate iodine intake. The major difference with respect to other studies is the low frequency of the biphasic form of PPT.     

Extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and c-Src are involved in gonadotropin-releasing hormone-stimulated activity of the glycoprotein hormone follicle-stimulating hormone beta-subunit promoter

The role of ERK, Jun N-terminal kinase (JNK), p38, and c-Src in GnRH-stimulated FSHbeta-subunit promoter activity was examined in the LbetaT-2 gonadotroph cell line. Incubation of the cells with a GnRH agonist resulted in activation of ERK, JNK, p38, and c-Src. The peak of ERK activation was observed at 5 min, whereas that of JNK, p38, and c-Src at 30 min, declining thereafter. ERK activation by GnRH is dependent on protein kinase C (PKC), as evident by activation, inhibition, and depletion of 12-O-tetradecanoylphorbol-13-acetate-sensitive PKC subspecies. Ca(2+) influx, but not Ca(2+) mobilization, is required for ERK activation. GnRH signaling to ERK is partially mediated by dynamin and a protein tyrosine kinase, apparently c-Src. ERK activation by GnRH in LbetaT-2 cells does not involve transactivation of epidermal growth factor receptor or mediation via Gbetagamma or beta-arrestin. Once activated by GnRH, ERK translocates to the nucleus. We examined the role of ERK, JNK, p38, and c-Src in GnRH-stimulated ovine FSHbeta promoter, linked to a luciferase reporter gene (-4741oFSHbeta-LUC). The PKC activator 12-O-tetradecanoylphorbol-13-acetate, but not the Ca(2+) ionophore ionomycin, stimulated FSHbeta-luciferase (LUC) activity. Furthermore, down-regulation of PKC, but not removal of Ca(2+), inhibited the GnRH response. Cotransfection of FSHbeta-LUC and the constitutively active forms of Raf-1 and MEK stimulated FSHbeta-LUC activity, whereas the dominant negatives of Ras, Raf-1, and MEK and the selective MEK inhibitor PD98059, abolished GnRH-induced FSHbeta-LUC activity. The dominant negatives of CDC42 and JNK reduced the GnRH response by 36 and 49%, respectively. Incubation of the cells with the p38 or the c-Src inhibitors SB203580 and PP1 also reduced the GnRH response. Surprisingly, two proximal activator protein-1 sites contribute very little to the GnRH response. Thus, PKC, ERK, JNK, p38, and c-Src, but not Ca(2+), are involved in GnRH induction of the ovine FSHbeta gene.     

The effect of drill-generated noise in the contralateral healthy ear following mastoid surgery: The emphasis on hearing threshold recovery time

In mastoid surgeries, contralateral ear noise exposure is a known, identified factor leading to high-frequency hearing loss due to the wide variety of surgical devices that may be used during the surgery. However, the hearing threshold recovery time after this trauma was uncertain. The present study aimed to assess this time. In this prospective survival analysis study, 28 consecutive patients with chronic otitis media who were undergoing tympanomastoidectomy were assessed. Standard pure-tone audiometry (PTA) and distortion-product otoacoustic emission (DPOAE) were measured in all contralateral ears before and 6 h, 24 h, 48 h, 72 h, and 96 h after the surgery. Based on the PTA postoperative hearing loss, survival rates at frequencies of 3000 Hz, 4000 Hz, 6000 Hz, and 8000 Hz were 44.4%, 36.4%, 51.7%, and 47.4%, 24 h after surgery; 11.1%, 9.1%, 10.3%, and 13.2%, 48 h after surgery; and 0%, 0%, 3.4%, and 2.6%, 72 h after surgery, respectively. Based on the PTA and DPOAE, survival rates at all frequencies were 0%, 96 h after the surgery. According to the PTA, mean hearing recovery times were 61.98 ± 26.76 h (3000 Hz), 62.73 ± 26.50 h (4000 Hz), 67.08 ± 25.90 h (6000 Hz), 70.70 ± 24.13 h (8000 Hz), and with regard to DPOAE the recovery times were 58.58 ± 28.39 h (2000 Hz), 63.32 ± 28.83 h (4000 Hz), 65.22 ± 29.13 h (6000 Hz), and 75.14 ± 22.70 h (8000 Hz), respectively. To conclude, high-frequency hearing loss usually occurs following mastoid surgeries that is mainly temporary and reversible after 72 h.     

Modification of Resistance to Streptococcus pneumoniae by Dietary Ethanol, Immunization, and Murine Retroviral Infection

Hallmarks of the acquired immune deficiency syndrome (AIDS) are immunologic alterations, frequently associated with opportunistic infections. To study such associations, LP-BM5 murine retrovirus infection was used as a murine model of AIDS. Retrovirally infected and uninfected mice were fed a 5% (v/v) ethanol diet for 55 days and then fed a 7% v/v ethanol diet for the final 7 days to assert the role of ethanol as a cofactor in development of murine AIDS. There was a reduction in polymorphonuclear neutrophils count in ethanol-fed groups. Neutrophils increased in retrovirus-infected groups, except those vaccinated 10 days before challenge with live bacteria. The percentage of splenic lymphocytes in the retrovirus-infected group was reduced in comparison with controls. Survival of the mice challenged intraperitoneally with Streptococcus pneumoniae was increased by vaccination and suppressed by dietary alcohol. Retrovirus infection caused a much faster death rate after bacterial challenge than nonretrovirus infected controls. Vaccination played an important role in delaying the death rate in all treated groups. Transferring spleen cells from healthy, unimmunized mice also enabled the retrovirally infected mice to survive the bacterial infection longer. Enhancement of resistance to S. pneumoniae by vaccination and transfer of immunocompetent cells to mice immunosuppressed by retroviral infection show the potential to use immunomodulation to affect disease resistance in AIDS.     

mTOR signaling: implications for cancer and anticancer therapy

Mounting evidence links deregulated protein synthesis to tumorigenesis via the translation initiation factor complex eIF4F. Components of this complex are often overexpressed in a large number of cancers and promote malignant transformation in experimental systems. mTOR affects the activity of the eIF4F complex by phosphorylating repressors of the eIF4F complex, the eIF4E binding proteins. The immunosuppressant rapamycin specifically inhibits mTOR activity and retards cancer growth. Importantly, mutations in upstream negative regulators of mTOR cause hamartomas, haemangiomas, and cancers that are sensitive to rapamycin treatment. Such mutations lead to increased eIF4F formation and consequently to enhanced translation initiation and cell growth. Thus, inhibition of translation initiation through targeting the mTOR-signalling pathway is emerging as a promising therapeutic option.     

Alcohol and Murine Acquired Immunodeficiency Syndrome Suppression of Resistance to Cryptosporidium parvum Infection during Modulation of Cytokine Production

The effects of inoculation of LP-BM5 murine leukemia retrovirus and chronic ethanol (5% v/v) ingestion on immunomodulation and Cryptosporidium parvum infection in C57BL/6 female mice were evaluated. The intestinal mucosae of retrovirally immunosuppressed animals were heavily colonized by Cryptosporidium parasites, and oocysts shedding in the feces persisted throughout the duration of the study. Mortality was exacerbated by murine retrovirus infection alone and exacerbated with concomitant chronic alcohol feeding (42.8 and 69.4%). Chronic ethanol ingestion decreased production of interferon-γ and soluble interleukin-2 receptor released in supernatants of splenocytes when stimulated with concanavalin A, compared with the control group. Decreased production of interferon-γ and interleukin-2 receptor was further exacerbated due to retrovirus infection. Tumor necrosis factor production by splenocytes stimulated with lipopolysaccharide, however, was significantly increased because of retrovirus infection. LP-BM5 retrovirus infection alone as well as with concomitant ethanol feeding altered cytokine production, which might have led to immunodeficiency. These changes may help explain the enhanced persistence of Cryptosporidiosis.     

Rates of protein synthesis--a review

The rates of protein synthesis can be measured by a variety of methods including pulse labeling, massive precursor administration, Scornik method, continuous feeding of labeled precursor, infusion, and pellet implantation. Each technique has some advantages and disadvantages. Massive precursor administration and infusion are the most widely used. The advantage of massive precursor administration is its simplicity, however, the amino acid concentration used is much higher than physiological levels. Infusion, however, is much more complicated as a technique and requires complicated calculations. The synthesis rates can also be calculated from degradation curves. Some of the above techniques can be used both in vivo and in vitro, and also for different organs (Shahbazian et al. (1987), Int. J. Dev. Neurosci., 5: 39-42). The brain has rapid rates of protein synthesis both in vivo and in vitro, the latter being much lower for adults.     

The complications of full-pelvic irradiation with particular emphasis to external beam therapy.

62 Patients with uterine carcinoma of cervix treated with high-dose large-volume full-pelvic irradiation given through co-axial-opposing pair portals over the anterior and posterior pelvis. Of these patients, 29 also received a single course of intracavitary radium supplementary to external beam irradiation. Only the severe complications which required surgical intervention have been analyzed, In the group of 33 patients who received only external irradiation, 4 developed such complications (12.1%).The overall incidence of those complications was about 19.3%. It is concluded that the treatment with hidh-dose large-volume full-pelvic irradiation technique, utilizing two opposing parallel pelvic portals, carries an incidence of morbidity 3-4 times the acceptable level and should be discouraged. Alternative techniques are discussed.