The paraventricular nucleus of hypothalamus mediates the pressor response to noradrenergic stimulation of the medial prefrontal cortex in unanesthetized rats

The medial prefrontal cortex (MPFC) is a structure that is also involved in cardiovascular modulation. The injection of norepinephrine (NE) into the prelimbic (PL) area of the MPFC of unanesthetized rats evokes a pressor response which is mediated by acute vasopressin release. Vasopressin is synthesized by magnocellular cells of the paraventricular (PVN) and supraoptic nucleus (SON) of the hypothalamus. In the present study, we endeavored to determine which vasopressin-synthesizing hypothalamic nucleus is involved in the pressor pathway activated after NE injection into the PL area of the MPFC. We report here that lidocaine microinjection into the SON did not change the pressor response evoked by NE injection into the PL. However, the response to NE was blocked by prior injection of lidocaine or CoCl₂ into the PVN, indicating that this area is responsible for the mediation of this pressor response. A neuroanatomic experiment in which the neuronal tracer biotinylated dextran amine (BDA) was microinjected into the MPFC showed a lack of axons or neuronal cell bodies in the PVN, indicating that there are no direct connections between the PL area of the MPFC and the PVN. The results suggest that the PVN is involved in the mediation of the pressor response to NE in the PL area and that this pathway must relay in other brain structures before reaching the PVN.     

Pressor effects of the injection of noradrenaline into different cerebroventricular spaces in unanesthetized rats

Injection of noradrenaline (NA) into the lateral cerebral ventricle (i.c.v.) was reported to cause blood pressure increase in unanesthetized rats, blocked by i.v. injection of vasopressin antagonists. We report similar responses to NA injection into the III or IV ventricles, suggesting multiple sites of action for i.c.v. NA. These responses were blocked by i.v. pretreatment with vasopressin antagonist, suggesting a common mediation by vasopressin release into circulation. Selected ventricular spaces were occluded with Nivea^® cream plugs to identify ventricular areas responding to i.c.v. NA. III ventricle or aqueduct occlusions markedly reduced pressor responses to i.c.v. NA. Microinjection of NA into the periaqueductal gray matter (PAG) caused pressor responses that were similar to those of i.c.v. NA, reinforcing the idea of a site of action in the aqueduct. IV ventricle occlusion only partially blocked the response to i.c.v. NA. The results suggest at least two sites of action for i.c.v. NA in unanesthetized rats. A primary site located in the PAG and another on the IV ventricle wall.     

Caffeine ingestion improves specific artistic swimming tasks

The main movements of artistic swimming demand various physical capacities such as flexibility, strength, power, and muscular endurance. The use of ergogenic resources to potentialize performance in this sport, however, is underexplored and deserves investigation. In the present study, we tested whether caffeine ingestion would improve the execution of movements that are essential in a typical figure competition or routines in artistic swimming (i.e., amplitude in the Ariana, height in the Boost and Barracuda, and time maintained in the Stationary Scull techniques). Sixteen experienced female athlete artistic swimmers (17.4±3.2 years of age, 5.6±2.8 years of artistic swimming practice) performed several movements of artistic swimming after having ingested a capsule containing caffeine (5 mg/kg body mass) or cellulose (placebo). Compared to the placebo, caffeine improved latero-lateral amplitude during the Ariana (P=0.035), the height of the Boost and Barracuda (P=0.028 and 0.009), and maintained duration in Stationary Sculling (P=0.012). Bayes factor analysis, however, indicated substantial evidence of a positive effect of caffeine only on the Barracuda and Stationary Scull techniques. These findings indicated that caffeine improved performance during specific artistic swimming movements. Coaches and athletes should consider caffeine ingestion in their supplementation plans.     

Primary myelofibrosis: risk stratification by IPSS identifies patients with poor clinical outcome

OBJECTIVES:

To evaluate whether risk scores used to classify patients with primary myelofibrosis and JAK-2 V617F mutation status can predict clinical outcome.

METHODS:

A review of clinical and laboratory data from 74 patients with primary myelofibrosis diagnosed between 1992 and 2011. The IPSS and Lille scores were calculated for risk stratification and correlated with overall survival.

RESULTS:

A V617F JAK2 mutation was detected in 32 cases (47%), with no significant correlation with overall survival. The patients were classified according to the scores: Lille - low, 53 (73.%); intermediate, 13 (18%); and high, 5 (7%); and IPSS – low, 15 (26%); intermediate-1, 23 (32%); intermediate-2, 19 (26%); and high, 15 (31%). Those patients presenting a higher risk according to the IPSS (high and intermediate-2) had a significantly shorter overall survival relative to the low risk groups (intermediate-1 and low) (p = 0.02).

CONCLUSIONS:

These results emphasize the importance of the IPSS prognostic score for risk assessment in predicting the clinical outcome of primary myelofibrosis patients.     

Antioxidant treatment prevented late memory impairment in an animal model of sepsis

OBJECTIVE: Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation. SUBJECTS: Male Wistar rats. INTERVENTIONS: Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. MEASUREMENTS AND MAIN RESULTS: On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction. CONCLUSIONS: Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.     

Potential therapeutic approaches for prevention and treatment of diabetic nephropathy and neuropathy: evidences of cilostazol

Cilostazol, a selective phosphodiesterase type III inhibitor, has vasodilatory, antiplatelet, and antithrombotic actions, as well as being the first-choice drug for the intermittent claudication due to peripheral vascular disease. Main researches have demonstrated significant improvement for this situation, including patients with diabetes mellitus, concerning pain-free walking distance and quality-of-life, not rising the bleeding event risk. It does not affect the glucose metabolism even in patients suffering from diabetes. This paper aims to present a review on the discoveries of various studies, most of them experimental, on the prevention and treatment of diabetes mellitus complications, such as nephropathy and neuropathy, through the use of cilostazol, which demonstrated satisfactory results on the improvement in neural blood flow, on sodium-potassium ATPase activity, on insulin resistance, and microalbuminuria. However, strict controlling of glucose plasma levels, hypertension, and smoking habits, as well as more extended investigations on the matter are required to the better comprehension.     

Chronic Administration of Ketamine Elicits Antidepressant‐Like Effects in Rats without Affecting Hippocampal Brain‐Derived Neurotrophic Factor Protein Levels

Abstract: A growing body of evidence has pointed to the blockade of the N‐methyl‐d ‐aspartate (NMDA) receptor signaling as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open‐field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain‐derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine‐ and ketamine‐treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders.     

Effects of a leucine-rich diet on body composition during nutritional recovery in rats

OBJECTIVE: Protein malnutrition is characterized by a number of morphologic and physiologic alterations, including intestinal mucosal atrophy and impaired nutrient absorption. Impaired absorption accentuates nutritional deficiency and accelerates body weight loss and changes in body chemistry. Because leucine is a ketogenic and oxidative amino acid and stimulates the protein synthesis, we examined the ability of young rats to recover from protein malnutrition by feeding them a control balanced or a leucine-rich diet for 60 d. METHODS: At the end of the 60-d period, body, liver, and muscle weights; glucose, methionine, and leucine intestinal absorption; and carcass chemical composition were evaluated. RESULTS: Body weight gain was higher in the control balanced and leucine-rich groups than in control rats, indicating that adequate refeeding allows body weight to recover in these groups. Methionine and glucose absorptions were impaired in malnourished rats but were restored after nutritional recovery. The leucine-rich diet resulted in an increase in carcass collagen nitrogen but maintained the carcass structural nitrogen. CONCLUSIONS: These results indicated that leucine supplementation during nutritional recovery from protein malnutrition improves protein carcass restoration. However, the precise mechanism of the leucine effects involved in this response remains to be elucidated.