Differential response of A 68930 and sulpiride in stress-induced gastric ulcers in rats

Dopamine is linked to gastrointestinal functions. However, its exact nature in stress-induced gastric pathology is still not clear. In the present study, an attempt has been made to identify the effects of dopamine in stress-induced gastric ulcers, and concurrent alterations in various ulcer-influencing factors such as plasma corticosterone levels, gastric mucosal PGE₂ content and proton pump activity. The dopamine D₁ receptor agonist (A 68930) and antagonist (SCH 23390), and D₂ receptor agonist (quinpirole) and antagonist (sulpiride) were used to evaluate their effects on acute stress (single immobilization for 150 min) and chronic unpredictable stress (two different types of stressors for 7 days) induced gastric ulcers in rats. Acute and chronic unpredictable stress significantly increased the gastric ulcer severity, adrenal hypertrophy and corticosterone levels, while gastric mucosal dopamine levels were decreased. Pretreatment of sulpiride (60 mg/kg) significantly reverted the acute stress-induced alterations, while A 68930 (0.25 mg/kg) significantly restored the acute and chronic unpredictable stress-induced alterations. In contrast, administration of SCH 23390 (0.1-0.5 mg/kg) and quinpirole (0.1-0.5 mg/kg) failed to alter acute stress-induced alterations. Further, A 68930 and sulpiride showed different response on proton pump inhibition under in-vitro condition. A 68930 (10-50 μg/ml) inhibited the gastric H⁺ K⁺-ATPase activity comparable to positive control omeprazole, while sulpiride (10-50 μg/ml) had no effect. A 68930 also normalized the decreased gastric PGE2 content observed during chronic unpredictable stress. The histopathological evaluation of gastric mucosal tissue supported the observations regarding the gastroprotective effect of sulpiride during acute stress and of A 68930 during both acute and chronic unpredictable stress conditions. Our results provide important insights into the mechanism of dopamine-regulated pathways, which cause an overall pathophysiology of gastric stress ulcers and implicating the importance of D₁ agonist in ulcer protection. Thus, current study highlights the need to evaluate anti-stress and anti-ulcer agents in terms of their ability to modulate dopaminergic transmissions.     

Health-related quality of life after chemotherapy cycle in breast cancer in Iran

The aim of this study was to compare the differences between the level of whole quality of life and its subscales after receiving two common treatment of breast cancer in women with early stage of breast cancer. A double-blinded cohort study was done in 100 breast cancer patients with node positive that used fluorouracil, doxorubicin, cyclophosphamide (FAC) and docetaxel, doxorubicin and cyclophosphamide (TAC) regimen as adjuvant therapy. Patients were followed for 4 months since the end of chemotherapy. Health-related quality of life was assessed using questionnaire (QLQ-C30) from European Organization for Research and Treatment of Cancer (EORTC). Independent t-test analysis was used at the significant level of 0.05 for analyzing the results. The mean of age was 48.49 ± 10.63 in these patients. QoL scores were 64 and 68 in TAC and FAC groups, respectively (P < 0.001). After 4 months, patients in TAC and FAC groups experienced 11.45 and 7.14 units of improvement in QoL scores, respectively (P = 0.02). Although, TAC had a more negative impact on QoL during chemotherapy, it created a higher improvement than FAC during 4 months since the end of treatment. These effects on quality of life should be considered in making decision for providing and financing cancer treatments in Iran.

     

A functional defect in the early phase of the immune response observed in patients with hemophilia A

In search of a functional immunological defect in patients with hemophilia A, we investigated the early phase of the immune response and found a deficiency in the monocyte-T cell interaction after in vitro exposure to a bacterial antigen. T-cell proliferation in response to Escherichia coli-pulsed autologous monocytes was significantly (P less than 0.025) reduced in hemophiliacs [mean dpm +/- SEM (n = 25): 9036 +/- 2600] as compared to healthy controls [mean dpm +/- SEM (n = 24): 17,812 +/- 2985]. This functional defect was expressed in a severe form (antigen-induced monocyte-T cell interaction less than or equal to 2000 dpm) in both HTLV III antibody-positive and -negative patient populations. Significantly decreased T-helper/T-suppressor-cell ratios (mean dpm +/- SEM: patients 1.47 +/- 0.13; controls 2.04 +/- 0.11; P less than 0.001)--but without a concomitant reduction in the absolute number of T-helper cells--could also be observed.     

Measurements of temperature generated by ultrasonic file in vitro

The temperature rise of the irrigant in the root canal during free vibration of the ultrasonic file was studied in vitro in 10 human teeth. The mean temperature rise was found to be 0.6 degrees C. The minimal temperature increase may not significantly contribute to the effectiveness of ultrasonic root canal instrumentation.     

Novel facile synthesis of imidazo[1,2-<Emphasis Type="Italic">b</Emphasis>]-[1,2,4,5]tetrazines with potential antimicrobial activity

Starting from 1-amino-2-methylthio-4-phenylimidazole 2, a series of the title compounds have been synthesized via its reactions with various hydrazonoyl halides 3. The mechanism of the reactions studied is discussed. The structure of the compounds prepared were elucidated on the basis of their elemental analyses, spectral data and alternate synthesis. The antimicrobial activities of the compounds prepared were screened and the results showed that most of such compounds exhibit considerable activities.     

Characterization of mother-infant HIV type 1 gag p17 sequences associated with perinatal transmission.

The gag p17 matrix sequences of human immunodeficiency virus type 1 (HIV-1) from seven infected mother-infant pairs were analyzed after perinatal transmission. The p17 matrix open reading frame was maintained in 143 of the 166 clones analyzed (86.2% frequency of intact p17 open reading frames). The functional domains essential for p17 matrix function in HIV-1 replication, including targeting of Gag to the plasma membrane, virus assembly and release, envelope glycoprotein incorporation into virus particle, virus entry, and localization of the virus preintegration complex to the nucleus of nondividing cells, were highly conserved in most of the sequences. In addition, examination of the three-dimensional structure of the p17 matrix protein in mother-infant isolates showed a high degree of conservation of amino acids required for correct folding and biological activity. Several amino acid motifs common to most of the mother-infant pairs sequences, including pair-specific signature sequences, were observed. There was a low degree of heterogeneity of gag p17 sequences within mothers, within infants, and between mother-infant pairs, but the distances were greater between epidemiologically unlinked individuals. Phylogenetic analyses of 166 mother-infant pairs and 181 other p17 sequences available from HIV-1 databases revealed distinct clusters for each mother-infant pair and for other p17 sequences. In conclusion, these findings indicate that an intact and functional gag p17 matrix is maintained during maternal-fetal transmission and that several motifs in p17 may be associated with perinatal transmission.