The effect of morphine sensitization on extracellular concentrations of GABA in dorsal hippocampus of male rats

Repeated, intermittent exposure to drugs of abuse, such as morphine results in response enhancements to subsequent drug treatments, a phenomenon referred to as behavioral sensitization. As persistent neuronal sensitization may contribute to the long-lasting consequences of drug abuse, characterizing the neurochemical mechanisms of sensitization is providing insights into addiction. Although it has been shown that GABAergic systems in the CA1 region of dorsal hippocampus are involved in morphine sensitization, the alteration of extracellular level of GABA in this area in morphine sensitization has not been investigated. In the present study, using the in vivo microdialysis technique, we investigated the effect of morphine sensitization on extracellular GABA concentration in CA1 region of dorsal hippocampus of freely moving rats. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular GABA concentration in CA1 was decreased following acute administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular GABA concentration in this area. The enhancement of GABA in morphine sensitized rats was inhibited by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the GABAergic neuronal transmission in dorsal hippocampus induced by morphine sensitization and it is implied that opioid receptors may play an important role in this effect.     

Significance of Platelet Count in Esophageal Carcinomas

Background/Aim:

Thrombocytosis is found to be associated with unfavorable prognosis in esophageal carcinoma. Platelets produce thymidine phosphorylase which is a platelet-derived endothelial cell growth factor with angiogenic activity. Increased platelet count may be translated into enhanced tumor growth. We examined the relation between platelet count and several prognostic variables in patients with esophageal cancer.

Patients and Methods:

Three hundred and eighty-one cases with esophageal cancer that underwent esophagectomy in a referral cancer institute during a 5-year period were studied retrospectively. The relation between preoperative platelet count and patient age, gender, site of tumor, presence of multiple cancers and clinicopathological characteristics including histological type, tumor size, depth of penetration (T), lymph node involvement (N), distant metastasis (M), degree of differentiation, presence of vascular, lymphatic and perineural invasion was examined.

Results:

Squamous cell carcinoma (SCC) constituted 93% and adenocarcinoma 7% of cases. Most of patients were in stage III, followed by stage II. The mean platelet count was 245±76 (× 10⁹ /L). There was no statistically significant correlation between platelet counts with prognostic factors except a weak linear correlation between platelet count and and tumor size (P= 0.03, Pearson correlation coefficient: 0.16). Patients with adenocarcinoma had a higher platelet count than those with SCC (P= 0.003).

Conclusion:

Platelet count does not correlate with prognostic factors in esophageal cancer. However, it is significantly different between SCC and adenocarcinoma of esophagus.     

Combined effects of HIV and marijuana use on neurocognitive functioning and immune status

The current study examined the independent and combined effects of HIV and marijuana (MJ) use (no use, light use, and moderate-to-heavy use) on neurocognitive functioning among a convenience sample of HIV-positive (HIV+) and HIV-negative (HIV–) individuals recruited from HIV community care clinics and advertisements in the Greater Los Angeles area. MJ users consisted of individuals who reported regular use of MJ for at least 12 months, with last reported use within the past month. Participants included 89 HIV+ (n?=?55) and HIV– (n?=?34) individuals who were grouped into non-users, light users, and moderate-to-heavy users based on self-reported MJ use. Participants were administered a brief cognitive test battery and underwent laboratory testing for CD4 count and viral load. HIV+ individuals demonstrated lower performance on neurocognitive testing than controls, and moderate-to-heavy MJ users performed more poorly on neurocognitive testing than light users or non-users. Moderate-to-heavy HIV+ users performed significantly lower on learning/memory than HIV– moderate-to-heavy users (M_D?=??8.34; 95% CI: ?16.11 to ?0.56) as well as all other comparison groups. In the domain of verbal fluency, HIV+ light users outperformed HIV– light users (M_D?=?7.28; 95% CI: 1.62–12.39), but no HIV group differences were observed at other MJ use levels. HIV+ MJ users demonstrated lower viral load (M_D?=??0.58; 95% CI: ?1.30 to 0.14) and higher CD4 count than non-users (M_D?=?137.67; 95% CI: 9.48–265.85). The current study findings extend the literature by demonstrating the complex relationship between HIV status and MJ use on neurocognitive and clinical outcomes.     

Tachykinin regulation of basal synovial blood flow

1. Experiments were performed to investigate the role of endogenously released tachykinins in the regulation of blood flow to the rat knee joint. Synovial perfusion was assessed by laser Doppler perfusion imaging, which permitted spatial measurement of relative changes in perfusion from control (pre drug administration), expressed as the percentage change. Most experiments were performed on the exposed medial aspect of the knee joint capsule.
2. Neither the selective tachykinin NK₁ receptor antagonist, FK888, nor the selective tachykinin NK₂ receptor antagonist, SR48968, significantly influenced synovial blood flow at doses of 10⁻¹², 10⁻¹⁰ and 10⁻⁸ mol. However, topical co-administration of these agents produced significant dose-dependent reductions in basal synovial perfusion of 6.3±4.6, 12.0±3.4 and 19.9±2.6%, respectively; n=29. The non-selective tachykinin NK₁/NK₂ receptor antagonist, FK224, also produced significant (at 10⁻¹⁰ and 10⁻⁸ mol), but less potent, reductions in perfusion of 5.3±4.0, 8.4±2.2 and 5.9±2.8%, respectively; n=25.
3. Topical administration of the α₁-, α₂-adrenoceptor antagonist phenoxybenzamine elicited a 31.3±6.2% increase in blood flow which was substantially reduced to 10.4±3.8% by co-administration of the FK888 and SR48968 (both at 10⁻⁸ mol; n=8–13), suggesting that normally there is sympathetic vasoconstrictor ‘tone'' which is opposed by the vasodilator action of endogenous tachykinins.
4. One week after surgical interruption of the nerve supply to the knee joint, co-administration of FK888 and SR48968 (both at 10⁻⁸ mol) now produced slight vasodilatation (6.7±4.6%; n=9) which did not differ significantly from vehicle treatment. Depletion of tachykinins from sensory nerve fibres by systemic capsaicin administration also resulted in abolition of the vasoconstrictor effect of FK888 and SR48968 (both at 10⁻⁸ mol), with these agents only producing a slight vasodilatation (2.5±5.3%; n=6).
5. By use of a near infra-red laser source it was possible to image knee joint perfusion transcutaneously, the overlying skin being left intact. In this more physiological situation, close intra-arterial injection of the combination of FK888 and SR48968 (both at 10⁻⁸ mol) again elicited vasoconstriction (48.8±16.2% reduction in blood flow; n=4).
6. These results indicate that endogenous tachykinins may be continuously released from sensory fibres innervating the joint. Basal release of tachykinins could therefore be an important physiological influence opposing sympathetic vasoconstrictor tone.

     

Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial

Background

Oxidative stress has a key role in the pathogenesis of type II diabetes mellitus (T2DM) and its vascular complications. Antioxidant therapy has been suggested as a potential approach to blunt T2DM development and progression. The aim of this study was to assess the effects of supplementation with curcuminoids, which are natural polyphenolics from turmeric, on oxidative indices in diabetic individuals.

Methods

In this randomized double-blind placebo-controlled trial, 118 subjects with T2DM were randomized to curcuminoids (1000 mg/day co-administered with piperine 10 mg/day) or matching placebo for a period of 8 weeks. Serum total antioxidant capacity, superoxide dismutase (SOD) activities and malondialdehyde (MDA) concentrations were measured at baseline and after the supplementation period.

Results

Curcuminoids supplementation caused a significant elevation in serum total antioxidant capacity (TAC) (p < 0.001) and SOD activities (p < 0.001), while serum MDA levels were significantly reduced compared with the placebo group (p < 0.001). These results remained statistically significant after adjustment for potential confounders (baseline differences in body mass index and fasting serum insulin).

Conclusion

The present results support an antioxidant effect of curcuminoids supplementation in patients with T2DM, and call for future studies to assess the impact of these antioxidant effects on the occurrence of diabetic complications and cardiovascular endpoints.

     

Morphine sensitization increases the extracellular level of glutamate in CA1 of rat hippocampus via μ-opioid receptor

Repeated administration of abuse drugs such as morphine elicits a progressive enhancement of drug-induced behavioral responses, a phenomenon termed behavioral sensitization. These changes in behavior may reflect plastic changes requiring regulation of glutamatergic system in the brain. In this study, we investigated the effect of morphine sensitization on extracellular glutamate concentration in the hippocampus, a brain region rich in glutamatergic neurons. Sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days free of the opioid treatment. The results showed that extracellular glutamate concentration in the CA1 was decreased following administration of morphine in non-sensitized rats. However, morphine-induced behavioral sensitization significantly increased the extracellular glutamate concentration in this area. The enhancement of glutamate in morphine sensitized rats was prevented by administration of naloxone 30 min before each of three daily doses of morphine. These results suggest an adaptation of the glutamatergic neuronal transmission in the hippocampus after morphine sensitization and it is postulated that opioid receptors may play an important role in this effect.