Anesthetic preconditioning: effects on latency to ischemic injury in isolated hearts

BACKGROUND: Anesthetic preconditioning (APC) is protective for several aspects of cardiac function and structure, including left ventricular pressure, coronary flow, and infarction. APC may be protective, however, only if the duration of ischemia is within a certain, as yet undefined range. Brief ischemia causes minimal injury, and APC would be expected to provide little benefit. Conversely, very prolonged ischemia would ultimately cause serious injury with or without APC. Previous investigations used a constant ischemic time as the independent variable to assess ischemia-induced changes in dependent functional and structural variables. The purpose of the study was to define the critical limits of efficacy of APC by varying ischemic time. METHODS: Guinea pig hearts (Langendorff preparation; n = 96) underwent pretreatment with sevoflurane (APC) or no treatment (control), before global ischemia and 120 min reperfusion. Ischemia durations were 20, 25, 30, 35, 40, and 45 min. RESULTS: At 120 min reperfusion, developed (systolic-diastolic) left ventricular pressure was increased by APC compared with control for ischemia durations of 25-40 min. Infarction was decreased by APC for ischemia durations of 25-40 min, but not 20 or 45 min. APC improved coronary flow and vasodilator responses for all ischemia durations longer than 25 min, and decreased ventricular fibrillation on reperfusion for ischemia durations longer than 30 min. CONCLUSIONS: Although APC protects against vascular dysfunction and dysrhythmias after prolonged ischemia, protection against contractile dysfunction and infarction in this model is restricted to a range of ischemia durations of 25-40 min. These results suggest that APC may be effective in a subset of patients who have cardiac ischemia of intermediate duration.     

The homocamptothecin BN 80915 is a highly potent orally active topoisomerase I poison

BN 80915, a lead compound of the homocamptothecin (hCPT) family, has entered clinical trials. BN 80915 is a difluoro-hCPT where the six-membered alpha-hydroxylactone ring of camptothecin (CPT) is replaced by a seven-membered beta-hydroxylactone ring. Preclinical data reported here show that in spite of the modification to the crucial E-ring of CPTs, BN 80915 retains topoisomerase I poisoning activity as shown in living HT29 cells as well as in cell-free assays, where BN 80915 always performs better than SN-38 or TPT. In antiproliferative assays BN 80915 is also very potent as evidenced by IC50s values consistently lower than those of SN38 in sensitive cell lines as well as in their related multidrug-resistant lines overexpressing P-glycoprotein or multidrug resistance-associated protein. Furthermore, in human plasma, in contrast to CPT analogs, the hydrolysis of BN 80915 is slow, leading to improved plasma stability, and irreversible, thus avoiding toxicity related to the accumulation of active principle during excretion in the urinary tract. These findings may account for the good in vivo efficacy observed in PC3 xenograft experiments where BN 80915 administered orally at very low doses doubled the tumor growth delay in comparison to CPT-11 administered i.p. Altogether, these results strongly support further development of BN 80915.     

The use of a computer-assisted image-guided system (InstaTrak) in orbital surgery.

PURPOSE: To assess the usefulness of a computer-assisted image-guided system (CAIGS) as an intraoperative anatomical guide in performing orbital surgery. METHODS: Noncomparative interventional case series of 30 consecutive orbital procedures performed by one surgeon (J.G.C.) using the CAIGS (InstaTrak) for intraoperative anatomical guidance. RESULTS: The series consisted of 8 cases of orbital decompression, 8 cases of orbital fracture, 11 cases of tumor excision, 2 cases of orbital reconstruction for severe enophthalmos, and 1 case of drainage of an orbital abscess. The CAIGS (InstaTrak) was useful in providing adjunctive intraoperative guidance in all 30 orbital cases. CONCLUSION: The CAIGS (InstaTrak) system is a useful adjunctive tool in providing intraoperative anatomic guidance in a consecutive series of varied orbital operations.     

Alpha-adrenergic systems mediate chronic central AII hypertension in rats fed high sodium chloride diet from weaning.

Hypertension is elicited by chronic, low dose intracerebroventricular (ICV) angiotensin II (AII) infusion in rats raised from weaning on relatively high sodium chloride diet (250 mEq kg(-1) food). This experimental model of hypertension is dependent upon renal innervation and associated with neurogenic sodium retention. The present study determined whether this neurogenic ICV AII hypertension is mediated by central alpha-adrenoceptors. Rats were weaned at 21 days of age and fed a 1.5% (250 mg kg(-1) food) sodium chloride diet for 10-12 weeks. At adulthood, animals were instrumented with central nervous system (CNS) lateral ventricular cannulas, femoral artery and vein catheters and housed in metabolic pens for chronic study. Low dose ICV AII infusion (20 ng min(-1)) increased mean arterial pressure (MAP) from 121 +/- 4 to 140 +/- 6 mm Hg on the day of ICV infusion. This increase in arterial pressure was associated with 3 consecutive days of decreased urinary sodium excretion. Subsequent ICV alpha-adrenoceptor blockade with phentolamine (AII + phentolamine) abolished the pressor and antinatriuretic responses to low dose chronic ICV AII infusion. Resumption of ICV AII infusion alone increased in MAP toward pre-alpha-adrenergic blockade values (133 +/- 5 mm Hg) on day 8. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly different from control. This model of hypertension was not dependent on circulating plasma renin activity (PRA), since PRA decreased during ICV AII infusion. These data confirm that low dose ICV AII causes hypertension and sodium retention in rats raised from weaning on moderately elevated sodium intake. We conclude that AII mediated neurogenic hypertension and antinatriuresis is elicited by stimulation of AT1 receptors on neurons which interact with noradrenergic cell bodies in cardiovascular and autonomic centers that may modulate renal sympathetic outflow via alpha-adrenoceptors.     

Emergence of Mutations in the K13 Propeller Gene of Plasmodium falciparum Isolates from Dakar,Senegal, in 2013-2014

The kelch 13 (K13) propeller gene is associated with artemisinin resistance. In a previous work, there were no mutations found in 138 Plasmodium falciparum isolates collected in 2012 and 2013 from patients residing in Dakar, Senegal (M. Torrentino-Madamet et al., Malar J 13:472, 2014, http://dx.doi.org/10.1186/1475-2875-13-472). However, the N554H, Q613H, and V637I mutations were identified in the propeller region of K13 in 92 (5.5%) isolates in 2013 and 2014. There were five polymorphisms identified in the Plasmodium/Apicomplexa-specific domain (K123R, N137S, N142NN/NNN, T149S, and K189T/N).     

Influence of scapular position on the pressure pain threshold of the upper trapezius muscle region

A position of scapula depression will maintain the upper trapezius muscle region in a lengthened position, causing excessive strain. This strain could lead to peripheral nociceptive nerves sensitization in the affected area, changing the pressure pain threshold (PPT). Thus, people with a faulty alignment of scapular depression may have lower PPT levels in the upper trapezius region when compared to subjects with normal vertical scapular position. The purpose of this double‐blind study was to assess the influence of scapular position on the PPT of the upper trapezius region in a young healthy population. Fifty two physical therapy students of the Catholic University of Minas Gerais – PUC‐Minas, Brazil, with normal shoulder (NS group, n=26, 6 men and 20 women) or depressed shoulder (DS group, n=26, 6 men and 20 women) volunteered to participate in this study. An electronic pressure algometer was used to measure the PPT on the upper trapezius muscle region. The results showed a significant difference between groups, with the DS group (19.0±9.0N/cm²) demonstrated lower mean PPT values when compared to NS group (26.1±9.6N/cm²) (p<0.01). Our results showed that healthy young subjects with depressed scapula position had significant lower upper trapezius PPT values when compared to subjects with normal scapula position.     

Pharmacokinetics of Transfer of Azithromycin into the Breast Milk of African Mothers

Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in mostly single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid maximum-effect (E_max) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.)     

Epidemiology of the resistance of Mycobacterium tuberculosis to antituberculosis drugs at the main hospital in Dakar, Senegal. A 4-year retrospective study (2000-2003)

A retrospective study was carried out from January?2000 to December?2003 to assess the resistance of Mycobacterium tuberculosis to antituberculosis drugs and the impact of this on the treatment result. Two hundred and two patients' files were studied (average age: 36?years; sex-ratio: 1.7). Pulmonary localisation (85.7%) or extrapulmonary localisation (14.3%). HIV status is negative (71.3%), positive (10.8%) or unknown (17.9%). The overall recovery rate is 60.7% (61.4% in HIV-; 46.1% in HIV+), the rate of treatment failure is 2.7% (1.1% in HIV-; 15.4% in HIV+), the death rate due to tuberculosis is 6.3% (2.3% in HIV-; 23.1% in HIV+), and the rate of patients who disappeared from the system is 30.3% (35.2% in HIV-; 14.2% in HIV+). Hepatotoxicity that occurred during treatment is observed in 14.3% of cases (recovery: 56.2%; failure: 6.2%; lost from the system: 18.8%). Eighty-four percent of patients never received antituberculosis treatment (group?A) versus 15.8% of patients who had already received one or more antituberculosis drugs (group?B). The rates of resistance to isoniazid are 6.4% (A) and 12.5% (B), to rifampicin 1.7% (A) and 12.5% (B), to ethambutol 0.5% (A) and 0% (B), to streptomycin 24.1% (A) and 46.8% (B). The percentage of multiresistant strains is 1% in patients not treated previously and 11% in those who had already received antituberculosis treatment. When the patients are carriers of a strain that is responsive to the treatment administered, the recovery rate is 64.2% versus 46.7% in patients whose strain is resistant to at least one of the treatments administered.