The mu opioid agonist DAMGO stimulates cAMP production in SK-N-SH cells through a PLC-PKC-Ca++ pathway

The mu-opioid agonist DAMGO exerts a dual activity on cAMP production in SK-N-SH neuroblastoma cells. While the classic inhibitory effect was prevented by pretreating the cells with pertussis toxin (PTX), the stimulatory activity was PTX-resistant. The stimulatory effect was abolished by the selective phospholipase C (PLC) blocker U-73122, by the selective protein kinase C (PKC) blocker chelerythrine and by the calcium-channels blockers Ni++, Co++ and Cd++. Hence, it is suggested that the opioid receptor activates PLC (probably through Gq GTP-binding proteins), to mobilize PKC, that positively modulates calcium channels in the plasma membrane; the entry of Ca++ into the cells stimulates calcium-activated adenylyl cyclases to produce cAMP.     

Beneficial effect of donepezil augmentation for the management of comorbid schizophrenia and dementia

Comorbid schizophrenia and dementia is a common clinical phenomenon; however, management of the coexisting illnesses remains incomplete. Donepezil, a cholinesterase inhibitor, may be beneficial for the management of symptoms of Alzheimer's disease, a disease in which cholinergic pathways in the cerebral cortex and basal forebrain are well known to be compromised. Furthermore, impaired cognition in elderly schizophrenic patients has been observed to be more than two thirds; however, there are no published controlled studies reporting the use of cholinesterase inhibitors in the management of schizophrenia in patients with associated dementia. In this study, six patients with chronic schizophrenia and comorbid dementia were administered donepezil, 5 mg, in single-blind fashion as augmentation to their standard antipsychotic medication for a 4-week period. Patients were evaluated with the Mini Mental State Examination (MMSE); Alzheimer's Disease Assessment Scale, Cognitive subscale; Positive and Negative Symptom Scale (PANSS); and the Clinical Global Impression (CGI) scales. A significant improvement was noted in MMSE scores (P < 0.01) and for CGI scores (P < 0.01). In addition, three patients demonstrated improvement on the PANSS. Donepezil appears to be an effective treatment for the management of symptoms of dementia accompanying patients with comorbid schizophrenia and dementia. Since cholinergic dysfunction may be present in some patients with schizophrenia, the authors' findings further demonstrate the possibility that this disorder may be managed with cholinergic medications as augmenting agents, at least in this specific subpopulation of patients with comorbid dementia. To confirm the findings of this preliminary trial, further investigation is mandated with a larger sample of subjects in the context of a double-blind medication trial.     

Laser-assisted uvulopalatoplasty revisited

When performed correctly in a properly selected patient, LAUP provides good and lasting results in snoring improvement. A sleep study with snoring analysis helps in patient selection. Laser-assisted uvulopalatoplasty can be performed adequately in one sitting.     

HsCRP levels: measurement of airway inflammation in asthmatic children.

BACKGROUND: The inflammatory marker, high-sensitivity C-reactive protein (HsCRP), is known to be related to non-allergic asthma, obesity, cardiovascular disease and smoking in adults. The aim of the present study was to determine whether HsCRP is related to respiratory symptoms and pulmonary function test findings in asthmatic children. METHODS: HsCRP was measured in 63 asthmatic children aged 2-12 years. The measurements were performed in 37 children during an episode of acute exacerbation and in 42 children during remission. RESULTS: HsCRP level (14.28 +/- 8.45 mg/L) during exacerbation was significantly higher than the mean level (1.92 +/- 3.16 mg/L) during remission (P < 0.0001), with the decrease being more prominent in children with a low body mass index percentile (P < 0.05). A reciprocal relationship was found between forced expiratory volume in 1 s and high-sensitivity C-reactive protein values (P > 0.049). CONCLUSION: Elevated HsCRP levels were significantly associated with respiratory impairment in children.     

Paediatric Behçet disease manifested as recurrent myositis: from an incomplete to a full-blown form

A 12-year-old boy presented with a limp and findings suggesting localised myositis of his right calf and a working diagnosis of Behçet disease was made. During 3 years of follow-up, he had another three episodes of calf myositis, all responsive to corticosteroids within days. Conclusion A case of recurrent localised myositis as a main manifestation of Behçet disease is reported. The evolution of incomplete Behçet disease, which is common in children, to the full blown form, with the emphasis on muscle involvement and the importance of early diagnosis of Behçet disease, is discussed.     

Association between alopecia and response to chemotherapy in patients with Hodgkin lymphoma

Alopecia and bone marrow suppression are prominent effects of doxorubicin-containing chemotherapy. The aim of the study was to validate our preliminary clinical observation that the lack of alopecia in Hodgkin lymphoma patients may predict poor response to chemotherapy and low rate of bone marrow suppression. Sixty-six patients with Hodgkin lymphoma were reviewed. They were treated between 1991 and 2001 with at least 4 courses of doxorubicin-containing chemotherapy (MOPP/ABV or ABVD) in 2 university-affiliated hematology departments. Thirty-four patients exhibited complete or near complete alopecia, and 32 retained their hair or had only minimal hair loss. The 2 groups were compared by response to treatment and episodes of bone marrow suppression. Alopecia was associated with a high rate of remission (OR 8.48, 95% CI 2.77-25.95), episodes of neutropenia (OR 3.55, 95% CI 1.28-9.84), leukopenia (OR 1.83, 95% CI 0.68-4.92), delays in scheduled treatments (OR 1.61, 95% CI 0.607-4.30), or number of courses with dose reduction (OR 1.63, 95% CI 0.56-4.74). Significantly more patients with alopecia had at least 1 of these parameters (88% versus 62%, P=0.015; OR 4.50, 95% CI 1.27-15.94). In conclusion, in patients with Hodgkin lymphoma treated with doxorubicin-containing chemotherapy, the absence of alopecia may predict poor response to treatment along with fewer episodes of bone marrow suppression. The absence of alopecia in such patients should alert clinicians to the possibility of treatment failure.     

Cannabinoids: between neuroprotection and neurotoxicity

Cannabinoids, such as the delta9-tetrahydrocannabinol (THC), present in the cannabis plant, as well as anandamide and 2-arachidonoyl glycerol, produced by the mammalian body, have been shown to protect the brain from various insults and to improve several neurodegenerative diseases. The current review summarizes the evidence for cannabinoid neuroprotection in vivo, and refers to recent in vitro studies, which help elucidate possible molecular mechanisms underlying this protective effect. Some of these mechanisms involve the activation of CB1 and CB2 cannabinoid receptors, while others are not dependent on them. In some cases, protection is due to a direct effect of the cannabinoids on neuronal cells, while in others, it results from their effects on non-neuronal elements within the brain. In many experimental set-ups, cannabinoid neurotoxicity, particularly by THC, resides side by side with neuroprotection. The current review attempts to shed light on this dual activity, and to dissociate between the two contradictory effects.     

Triclabendazole Effect on Protease Enzyme Activity in the Excretory- Secretory Products of Fasciola hepatica in Vitro

Background

Fasciola hepatica is one of the most important helminthes parasites and triclabendazole (TCBZ) is routinely used for treatment of infected people and animals. Secreted protease enzymes by the F. hepatica plays a critical role in the invasion, migration, nutrition and the survival of parasite and are key targets for novel drugs and vaccines. The aim of study was to determine the protease activity of excretory- secretory products (ESP) of F. hepatica in the presence of TCBZ anthelmintic.

Methods

F. hepatica helminthes were collected and cultured within RPMI 1640 [TCBZ treated (test) and untreated (control)] for 6 h at 37 °C. ESP of treated and control were collected, centrifuged and supernatants were stored at -20°C. Protein concentrations were measured according to Bradford method. Protease enzymes activities of ESP samples were estimated by using sigma’s non-specific protease activity assay. ESP protein bands were detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Results

Mean protein concentrations in control and treated of ESP samples were determined 196.1 ±14.52 and 376.4 ±28.20 μg/ml, respectively. Mean protease enzymes activities in control and treated were 0.37 ±0.1 and 0.089 ±0.03 U/ml, respectively. Significant difference between proteins concentrations and protease enzymes activities of two groups was observed (P<0.05). SDS-PAGE showed different patterns of protein bands between treated and control samples.

Conclusion

The TCBZ reduced secreted protease enzymes activities and possibly effects on invasion, migration, nutrition and particularly survival of the parasite in the host tissues.     

Methicillin-Resistant Staphylococcus aureus Sequence Type 239-III, Ohio, USA, 2007�C2009

Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen that has diverse molecular heterogeneity. Most MRSA strains in the United States are pulsed-field gel electrophoresis USA100 sequence type (ST) 5 and USA300 ST8. Infections with MRSA ST239-III are common and found during health care–associated outbreaks. However, this strain has been rarely reported in the United States. As part of a study supported by the Prevention Epicenter Program of the Centers for Disease Control and Prevention (Atlanta, GA, USA), which evaluated transmission of MRSA among hospitals in Ohio, molecular typing identified 78 (6%) of 1,286 patients with MRSA ST239-III infections. Ninety-five percent (74/78) of these infections were health care associated, and 65% (51/78) of patients had histories of invasive device use. The crude case-fatality rate was 22% (17/78). Identification of these strains, which belong to a virulent clonal group, emphasizes the need for molecular surveillance.Staphylococcus aureus is a major human pathogen that possesses multiple toxins and virulence mechanisms (1). Antimicrobial drug resistance in S. aureus has added to the complexity of treating serious infections caused by this bacteria, and methicillin-resistant S. aureus (MRSA) appears to have greater virulence than methicillin-susceptible strains (2,3). Most MRSA strains in the United States are pulsed-field gel electrophoresis (PFGE) types USA100 and USA300, corresponding to multilocus sequence typing (MLST) ST5 and ST8, respectively (4). MRSA belonging to MLST ST239 and harboring staphylococcal cassette chromosome mec (SCCmec) type III (MRSA ST239-III) are associated with infections in health care settings, outbreaks, increased resistance to antimicrobial drugs, and capacity for invasive disease (5–7).MRSA ST239-III has a history of successful dissemination in many regions, leading to a diverse array of regionally prevalent clones. These clones include the Brazilian; British Epidemic 1, 4, 7, 9, and 11; Canadian Epidemic 3/Punjab; Czech; Eastern Australian 2 and 3; Georgian; Hungarian; Lublin; Nanjing/Taipei (ST241); Portuguese; and Vienna clones (8,9). Although it is common worldwide, MRSA ST239-III has not played any predominant role in the United States; infections with MRSA ST239-III have been rarely reported in the United States since the 1990s (9–13). Recently, only 2 reports of this strain in the United States involving sporadic nasal colonization and bloodstream infections have been published (13,14).In this study, we describe clinical epidemiologic characteristics and molecular analysis of clinical infections with MRSA ST239-III in the midwestern United States. Identification of a strain from such a virulent clonal group in the United States with wide dissemination in other parts of the world represents a potential public health concern.     

Genetic models of abnormal apoptosis in lymphocytes

Summary: Apoptosis is a critical mechanism for regulating cell numbers during development, normal responses to hormones and other stimuli, and immune and inflammatory reactions. Recent advances in defining the biochemical mechanisms of cell death, and the development of animal models with isolated defects in cell death pathways, have led to an increasing appreciation of the pathophysiologic importance of lymphocyte apoptosis. In this article, we review our current understanding of the pathways and roles of apoptosis in lymphocytes, with an emphasis on trans-genic and knockout models. We also summarize the relevance of these animal models to human diseases.