Effect of depression treatment on depressive symptoms in older adulthood: the moderating role of pain

OBJECTIVES: To investigate whether pain severity and interference with normal work activities moderate the effects of depression treatment on changes in depressive symptoms over time in older adults in primary care. DESIGN: Patient-randomized, clinical trial. SETTING: Multisite: three clinics located in Veterans Affairs Medical Centers. PARTICIPANTS: Adults aged 60 and older (n=524) who screened positive for depression and participated in the Primary Care Research in Substance Abuse and Mental Health for the Elderly Study. INTERVENTION: Integrated care versus enhanced specialty referral care. MEASUREMENTS: Pain severity, the degree to which pain interferes with work inside and outside of the home, and depressive symptoms were examined at baseline and 3, 6, and 12 months. RESULTS: Intention-to-treat analyses revealed that both treatment groups showed reduced depressive symptoms over time, although self-reported pain moderated reductions in depressive symptoms. At higher levels of pain severity and interference with work activities, improvements in depressive symptoms were blunted. Furthermore, pain interference appeared to have a greater effect on depressive symptoms than did pain severity; in individuals with major depression, pain interference fully accounted for the moderating effects of pain severity on changes in depressive symptoms over time. CONCLUSION: Pain and its interference with functioning interfere with recovery from depression. Findings highlight the importance of addressing multiple domains of functioning (e.g., physical and social disability) and the degree to which pain and other forms of physical comorbidity may hinder or minimize treatment-related improvements in depressive symptoms.     

Blood beta-glucuronidase as a suitable biomarker at acute exposure of severe organophosphorus poisoning in human

Organophosphorus compounds are known to cause the selective release of liver microsomal beta-glucuronidase into plasma. Organophophoruses may induce nitrosative stress leading to the generation of nitrogen free radicals and alterations in scavengers of free radicals in many biological systems. In this study, we investigate how acute human organophosphorus intoxication is associated with changes of blood nitric oxide, total thiol molecules, and activities of the acetylcholinesterase and beta-glucuronidase. A total of 21 acute organophosphorus-poisoned patients were recruited into study and were divided into two groups of mildly (13) and severely affected (9); 26 age-matched healthy volunteers were recruited as control group. Results indicated that both mildly and severely affected patients had lower acetylcholinesterase activities as compared to controls. The extent of acetylcholinesterase reduction in the severely affected patients was higher than that of mildly affected patients. A significant increase in serum beta-glucuronidase was observed only in severely affected patients as compared to controls. Both mildly and severely affected patients had lower plasma total thiol molecules as compared to controls. The extent of reduction of total thiol molecules in the severely affected patients was higher than that of mildly affected patients. No significant difference was observed in plasma total nitric oxide of controls and patients. It is concluded that nitrosative stress has a minor role in toxicity of organophosphorus, whereas blood beta-glucuronidase is very sensitive biomarker at high exposure of severe organophosphorus poisoning.     

Safety evaluation of amylomaltase from Thermus aquaticus

A recombinant amylomaltase, MQ-01, obtained by cultivation of Bacillus subtilis expressing the amylomaltase gene from Thermus aquaticus is to be used in the production of enzymatically-synthesized glycogen; which is intended for use as a food ingredient. In order to establish the safety of MQ-01, the enzyme was subjected to standard toxicological testing. In a battery of standard Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) and in Escherichia coli WP2 uvrA, both with and without metabolic activation, MQ-01 failed to exhibit mutagenic activity. Similarly, MQ-01 did not display clastogenic properties in Chinese hamster lung fibroblast cells (CHL/IU), in an in vitro chromosomal aberration assay. In a 13-week subchronic toxicity study in rats, oral administration of MQ-01 at doses of up to 15 mL/kg body weight/day (corresponding to approximately 1230 mg/kg body weight/day) did not produce compound-related clinical signs or toxicity, changes in body weight gain, food consumption, hematology, clinical chemistry, urinalysis, organ weights, or in any gross and microscopic findings. The results of this study support the safety of MQ-01 in food production.     

Prevention of malathion-induced depletion of cardiac cells mitochondrial energy and free radical damage by a magnetic magnesium-carrying nanoparticle

The present work was designed to examine the effect of a new (25)Mg(2+)-carrying nanoparticle (PMC16) on energy and oxidative stress parameters inside the heart of the rats exposed to acute mild toxic dose of malathion, a widely used organophosphate. Post a single intraperitoneal (ip) injection of malathion (0.25 of LD50), PMC16 at different doses (0.05, 0.1, and 0.2 of LD50) was administered intravenously (iv) as a supplement to standard therapy of atropine and pralidoxime. MgSO(4) was used as another supplement for comparison with PMC16. Oxidative stress biomarkers including lipid peroxidation (LPO) and reactive oxygen species (ROS), antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), ATP/ADP ratio, and Mg in the cardiac cells were determined. Results indicated a significant increase in LPO, ROS, ADP/ATP ratio, and a decrease in Mg post-malathion poisoning in comparison to controls. All of these parameters were improved by use of standard therapy either with MgSO4 or various doses of PMC16. The activities of SOD, CAT, and GPx did not change significantly in the present acute malathion poisoning model and neither MgSO(4) or PMC16 had no considerable improvement on these parameters. Comparing groups that received normal Mg and those of various doses of PMC16, a significant difference was found with the PMC16 (0.2 LD50) group. PMC16 0.2 reduced cardiac cells LPO and ROS of Mal-exposed animals rather than that of MgSO4. PMC16 0.2 was also significantly better than MgSO(4) in improving MAL-induced changes in ADP/ATP ratio and also intracellular Mg levels. This study illustrates that malathion-induced cardiac cells toxicity is improved by administration of Mg as a result of increasing cardiac ATP through active transport of Mg inside the cells. Finally, the results of this study support positive effects of this magnetic Mg nanoparticle carrier but do not confirm its absolute efficacy that remains to be explored by further tests in different animal models and organs before moving to a phase I human trial.     

The effect of fresh frozen plasma in severe closed head injury

OBJECTIVE: Traumatic brain injury (TBI) is one of the most common causes of morbidity and mortality. Coagulopathy, commonly occurring after severe TBI, is associated with poor outcome and secondary complications, especially delayed traumatic intracerebral hematoma (DTICH). In this study we evaluated the effect of fresh frozen plasma (FFP) on the reduction in the incidence of DTICH in severe closed head injury victims. METHODS: This study was carried out as a double-blind randomized clinical trial. Ninety patients were entered in two parallel groups taking either FFP or normal saline (N/S). Patients' selection criteria for both groups were: severe closed head injury (Glasgow coma scale < or =8), no mass lesion required evacuation and no history of coagulopathy. The clinical findings, laboratory data, computed tomography (CT) scans and Glasgow outcome scale after 1 month were assessed and compared in two groups. RESULTS: Out of 90 patients, 44 received FFP and 46 received N/S. The development of new intracerebral hematoma in follow-up CT scans were more common in the FFP group than the N/S group (p=0.012). Both groups showed similar frequency of poor outcome (p=0.343). The mortality was significantly more common in the FFP group than in the N/S group (63% versus 35%, p=0.006). CONCLUSION: The result of this study revealed that early empirical infusion of FFP in patients with severe head injury may lead to adverse effects, such as an increase in the frequency of DTICH and an increase in the mortality.     

Role of ATP-sensitive potassium channels in the biphasic effects of morphine on pentylenetetrazole-induced seizure threshold in mice

Although several studies have indicated that the opioid receptor agonist morphine exerts biphasic effects on clonic seizure threshold, as yet little is known of the underlying mechanisms in this effect. In the present study, using the specific ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide and the specific K(ATP) channel opener cromakalim, the possible involvement of K(ATP) channels in the effects of morphine on pentylenetetrazole (PTZ)-induced seizure threshold in mice was investigated. Acute administration of lower doses of morphine (1, 3 and 7.5 mg/kg, i.p.) increased and higher doses of morphine (30 and 60 mg/kg, i.p.) decreased the PTZ-induced seizure threshold. Glibenclamide (2.5-5 mg/kg) increased the PTZ-induced seizure threshold. Non-effective dose of cromakalim (0.1 microg/kg) inhibited anticonvulsant effect of glibenclamide (5 mg/kg). Acute administration of non-effective dose of glibenclamide (1 mg/kg) interestingly inhibited both anticonvulsant and pro-convulsant effects of morphine and this effect was significantly reversed by cromakalim (0.1 microg/kg). These results support the involvement of K(ATP) channels in the modulation of seizure threshold by morphine.     

Estimating the relapse risk of Plasmodium vivax in Iran under national chemotherapy scheme using a novel method

OBJECTIVES: This study aimed to estimate the relapse risk of Plasmodium vivax under national chemotherapy scheme using a novel method, and assessed its pattern in Kahnooj, a malaria endemic area in Iran. METHODS: The authors traced repeated episodes of malaria attack between 1994 and 2001 and then, estimated the risks of secondary attack of P. vivax, classified by the species in their primary attack. It is suggested that the difference between the secondary attack rate in those who were infected by P falciparum and P. vivax in their primary attack may estimate the P. vivax relapse rate indirectly. RESULTS: This method showed that the relapse risk of P. vivax with in one and two years after the primary attack were 16.8 and 24.5% respectively. The risks of relapse before three or after 18 months were very low. INTERPRETATION & CONCLUSION: The relapse pattern of P. vivax was compatible with the dominant pattern in most of the temperate areas. In addition, the relapse risk was very close to the estimated relapse risks in clinical trials on anti-relapse drugs. Therefore, we concluded that the anti-relapse therapy in the study area was effective; also, this method may estimate the relapse risk of P. vivax accurately.