Isoflurane Modulates Cardiac Mitochondrial Bioenergetics by Selectively Attenuating Respiratory Complexes

Mitochondrial dysfunction contributes to cardiac ischemia–reperfusion (IR) injury but volatile anesthetics (VA) may alter mitochondrial function to trigger cardioprotection. We hypothesized that the VA isoflurane (ISO) mediates cardioprotection in part by altering the function of several respiratory and transport proteins involved in oxidative phosphorylation (OxPhos). To test this we used fluorescence spectrophotometry to measure the effects of ISO (0, 0.5, 1, 2 mM) on the time-course of interlinked mitochondrial bioenergetic variables during states 2, 3 and 4 respiration in the presence of either complex I substrate K+-pyruvate/malate (PM) or complex II substrate K+-succinate (SUC) at physiological levels of extra-matrix free Ca2 + (~ 200 nM) and Na+ (10 mM). To mimic ISO effects on mitochondrial functions and to clearly delineate the possible ISO targets, the observed actions of ISO were interpreted by comparing effects of ISO to those elicited by low concentrations of inhibitors that act at each respiratory complex, e.g. rotenone (ROT) at complex I or antimycin A (AA) at complex III. Our conclusions are based primarily on the similar responses of ISO and titrated concentrations of ETC. inhibitors during state 3. We found that with the substrate PM, ISO and ROT similarly decreased the magnitude of state 3 NADH oxidation and increased the duration of state 3 NADH oxidation, ΔΨm depolarization, and respiration in a concentration-dependent manner, whereas with substrate SUC, ISO and ROT decreased the duration of state 3 NADH oxidation, ΔΨm depolarization and respiration. Unlike AA, ISO reduced the magnitude of state 3 NADH oxidation with PM or SUC as substrate. With substrate SUC, after complete block of complex I with ROT, ISO and AA similarly increased the duration of state 3 ΔΨm depolarization and respiration. This study provides a mechanistic understanding in how ISO alters mitochondrial function in a way that may lead to cardioprotection

Enhanced charge-independent Mitochondrial Free Ca\u3csup\u3e2+\u3c/sup\u3e and Attenuated ADP-induced NADH Oxidation by Isoflurane: Implications for Cardioprotection

Modulation of mitochondrial free Ca2 + ([Ca2 +]m) is implicated as one of the possible upstream factors that initiates anesthetic-mediated cardioprotection against ischemia–reperfusion (IR) injury. To unravel possible mechanisms by which volatile anesthetics modulate [Ca2 +]m and mitochondrial bioenergetics, with implications for cardioprotection, experiments were conducted to spectrofluorometrically measure concentration-dependent effects of isoflurane (0.5, 1, 1.5, 2 mM) on the magnitudes and time-courses of [Ca2 +]m and mitochondrial redox state (NADH), membrane potential (ΔΨm), respiration, and matrix volume. Isolated mitochondria from rat hearts were energized with 10 mM Na+- or K+-pyruvate/malate (NaPM or KPM) or Na+-succinate (NaSuc) followed by additions of isoflurane, 0.5 mM CaCl2 (≈ 200 nM free Ca2 + with 1 mM EGTA buffer), and 250 μM ADP. Isoflurane stepwise: (a) increased [Ca2 +]m in state 2 with NaPM, but not with KPM substrate, despite an isoflurane-induced slight fall in ΔΨm and a mild matrix expansion, and (b) decreased NADH oxidation, respiration, ΔΨm, and matrix volume in state 3, while prolonging the duration of state 3 NADH oxidation, respiration, ΔΨm, and matrix contraction with PM substrates. These findings suggest that isoflurane\u27s effects are mediated in part at the mitochondrial level: (1) to enhance the net rate of state 2 Ca2 + uptake by inhibiting the Na+/Ca2 + exchanger (NCE), independent of changes in ΔΨm and matrix volume, and (2) to decrease the rates of state 3 electron transfer and ADP phosphorylation by inhibiting complex I. These direct effects of isoflurane to increase [Ca2 +]m, while depressing NCE activity and oxidative phosphorylation, could underlie the mechanisms by which isoflurane provides cardioprotection against IR injury at the mitochondrial level

Modulation of Mitochondrial Bioenergetics in the Isolated Guinea Pig Beating Heart by Potassium and Lidocaine Cardioplegia: Implications for Cardioprotection

Mitochondria are damaged by cardiac ischemia/reperfusion (I/R) injury but can contribute to cardioprotection. We tested if hyperkalemic cardioplegia (CP) and lidocaine (LID) differently modulate mitochondrial (m) bioenergetics and protect hearts against I/R injury. Guinea pig hearts (n = 71) were perfused with Krebs Ringer\u27s solution before perfusion for 1 minute just before ischemia with either CP (16 mM K+) or LID (1 mM) or Krebs Ringer\u27s (control, 4 mM K+). The 1-minute perfusion period assured treatment during ischemia but not on reperfusion. Cardiac function, NADH, FAD, m[Ca2+], and superoxide (reactive oxygen species) were assessed at baseline, during the 1-minute perfusion, and continuously during I/R. During the brief perfusion before ischemia, CP and LID decreased reactive oxygen species and increased NADH without changing m[Ca2+]. Additionally, CP decreased FAD. During ischemia, NADH was higher and reactive oxygen species was lower after CP and LID, whereas m[Ca2+] was lower only after LID. On reperfusion, NADH and FAD were more normalized, and m[Ca2+] and reactive oxygen species remained lower after CP and LID. Better functional recovery and smaller infarct size after CP and LID were accompanied by better mitochondrial function. These results suggest that mitochondria may be implicated, directly or indirectly, in protection by CP and LID against I/R injury

Evaluation of the long-term impact of the TOSTAN programme on the abandonment of FGM/C and early marriage: Results from a qualitative study in Senegal

In 1998–99, a village empowerment program was implemented in the Thiès/Fatick and Kolda regions of Senegal by the nongovernmental organization Tostan, to mobilize communities to hold public declarations in support of abandoning harmful traditional practices, including female genital mutilation/cutting (FGM/C) and child marriage. The information presented in this report indicates that many did end the practices following a public declaration, however, the lack of follow-up in the field and the absence of support mechanisms pose a large obstacle. Nevertheless, the program achieved significant results: knowledge of life skills resulting in positive changes and a shift in the perception of FGM/C moved everyone toward abandonment of this practice. Two main recommendations emerged from this retrospective assessment: 1) there is a need to provide support to these villages following the public declaration; and 2) there is a need to provide more support to families/communities that have abandoned the practice

Measuring Morbidity Associated with Urinary Schistosomiasis: Assessing Levels of Excreted Urine Albumin and Urinary Tract Pathologies

Urinary schistosomiasis is a debilitating disease caused by a parasitic worm that dwells in the blood vessels, particularly those surrounding the human bladder wall. Although not directly associated with high patient mortality, this disease is linked to both short-term morbidity, e.g. visible blood in urine (acute), as well as long-term sequelae, e.g. urinary tract pathologies (chronic). Numerous control programmes based upon chemotherapy have been implemented in sub-Saharan Africa in an attempt to reduce the burden of disease inflicted, particularly in children. Although there are rapid tests to assess the prevalence of acute manifestations of disease (i.e. blood in urine), namely urine-reagent strips, monitoring of chronic manifestations (i.e. urinary tract pathologies) is still rather laborious, time-consuming and requires specialised equipment, e.g. portable ultrasonography, as well as highly trained staff. This study has attempted to evaluate associations between albuminuria (albumin in urine, a new application for the HemoCue photometer) and urinary tract pathologies, and consequently assess this new biochemical marker as a potential rapid proxy of chronic disease sequelae typical in children in areas where urinary schistosomiasis is of public health importance

Oral iron acutely elevates bacterial growth in human serum.

Iron deficiency is the most common nutrient deficiency worldwide and routine supplementation is standard policy for pregnant mothers and children in most low-income countries. However, iron lies at the center of host-pathogen competition for nutritional resources and recent trials of iron administration in African and Asian children have resulted in significant excesses of serious adverse events including hospitalizations and deaths. Increased rates of malaria, respiratory infections, severe diarrhea and febrile illnesses of unknown origin have all been reported, but the mechanisms are unclear. We here investigated the ex vivo growth characteristics of exemplar sentinel bacteria in adult sera collected before and 4 h after oral supplementation with 2 mg/kg iron as ferrous sulfate. Escherichia coli, Yersinia enterocolitica and Salmonella enterica serovar Typhimurium (all gram-negative bacteria) and Staphylococcus epidermidis (gram-positive) showed markedly elevated growth in serum collected after iron supplementation. Growth rates were very strongly correlated with transferrin saturation (p < 0.0001 in all cases). Growth of Staphylococcus aureus, which preferentially scavenges heme iron, was unaffected. These data suggest that even modest oral supplements with highly soluble (non-physiological) iron, as typically used in low-income settings, could promote bacteremia by accelerating early phase bacterial growth prior to the induction of immune defenses

Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment of malaria in children (IPTc) is a promising new approach to the control of malaria in areas of seasonal malaria transmission but it is not known if IPTc adds to the protection provided by an insecticide-treated net (ITN). METHODS AND FINDINGS: An individually randomised, double-blind, placebo-controlled trial of seasonal IPTc was conducted in Burkina Faso in children aged 3 to 59 months who were provided with a long-lasting insecticide-treated bednet (LLIN). Three rounds of treatment with sulphadoxine pyrimethamine plus amodiaquine or placebos were given at monthly intervals during the malaria transmission season. Passive surveillance for malaria episodes was established, a cross-sectional survey was conducted at the end of the malaria transmission season, and use of ITNs was monitored during the intervention period. Incidence rates of malaria were compared using a Cox regression model and generalized linear models were fitted to examine the effect of IPTc on the prevalence of malaria infection, anaemia, and on anthropometric indicators. 3,052 children were screened and 3,014 were enrolled in the trial; 1,505 in the control arm and 1,509 in the intervention arm. Similar proportions of children in the two treatment arms were reported to sleep under an LLIN during the intervention period (93%). The incidence of malaria, defined as fever or history of fever with parasitaemia ≥ 5,000/µl, was 2.88 (95% confidence interval [CI] 2.70-3.06) per child during the intervention period in the control arm versus 0.87 (95% CI 0.78-0.97) in the intervention arm, a protective efficacy (PE) of 70% (95% CI 66%-74%) (p<0.001). There was a 69% (95% CI 6%-90%) reduction in incidence of severe malaria (p = 0.04) and a 46% (95% CI 7%-69%) (p = 0.03) reduction in the incidence of all-cause hospital admissions. IPTc reduced the prevalence of malaria infection at the end of the malaria transmission season by 73% (95% CI 68%-77%) (p<0.001) and that of moderately severe anaemia by 56% (95% CI 36%-70%) (p<0.001). IPTc reduced the risks of wasting (risk ratio [RR] = 0.79; 95% CI 0.65-1.00) (p = 0.05) and of being underweight (RR = 0.84; 95% CI 0.72-0.99) (p = 0.03). Children who received IPTc were 2.8 (95% CI 2.3-3.5) (p<0.001) times more likely to vomit than children who received placebo but no drug-related serious adverse event was recorded. CONCLUSIONS: IPT of malaria provides substantial protection against malaria in children who sleep under an ITN. There is now strong evidence to support the integration of IPTc into malaria control strategies in areas of seasonal malaria transmission. TRIAL REGISTRATION: ClinicalTrials.govNCT00738946. Please see later in the article for the Editors' Summary

Evaluation of groundnut genotypes for field resistance to seed infection by Aspergillus flavus and to aflatoxin contamination: Report of Work Done During May 1988 - April 1989

Twenty-one groundnut genotypes reported resistant and susceptible to in vitro seed colonization by Aspergillus flavus were tested for field resistance to seed infection, particularly preharvest infection by the aflatoxigenic fungus, and for aflatoxin contamination....

Trypanosomosis in The Gambia: prevalence in working horses and donkeys detected by whole genome amplification and PCR, and evidence for interactions between trypanosome species

<p>Abstract</p> <p>Background</p> <p>The Gambia has an increasing population of <it>equidae </it>largely used for agriculture and transportation. A review of cases at The Gambian Horse and Donkey Trust (GHDT) indicated that a common reason for presentation is a poorly defined medical condition often attributed to trypanosomosis. There are few reports describing the prevalence or the range of clinical signs associated with infection with different species of trypanosomes in horses and donkeys, but given the importance of these animals, the role of trypanosomosis requires investigation.</p> <p>Results</p> <p>In total 241 animals from the Central River Division in The Gambia (183 horses and 58 donkeys) were screened using Whole Genome Amplification (WGA) followed by trypanosome species identification using polymerase chain reaction (PCR). The results indicated overall trypanosome prevalence of 91%; with an infection rate of 31% for <it>Trypanosoma congolense </it>Savannah, 87% for <it>Trypanosoma vivax </it>and 18% for <it>Trypanosoma brucei </it>sp. Multiple species were present in 43% of infections. Microscopy had a good specificity (100%) and positive predictive value (100%) for trypanosome detection, but the sensitivity (20%) and negative predictive value (10.5%) were low relative to PCR-based diagnosis.</p> <p>Infection with <it>T congolense </it>showed the greatest negative effect on packed cell volume (PCV), while infection with <it>T. brucei </it>sp also had a significant, although lesser, negative effect on PCV. In addition, cases positive by microscopy were associated with significantly lower PCV. However, concurrent infection with <it>T. vivax </it>appeared to cause less effect on PCV, compared to animals infected with <it>T. congolense </it>alone.</p> <p>Conclusion</p> <p>The prevalence of Trypanosomosis was high in both horses and donkeys. Infection with <it>T. congolense </it>appeared to have the greatest clinical significance, while <it>T. vivax </it>infection may be of limited clinical significance in this population. Indeed, there is evidence of <it>T. vivax </it>co-infection ameliorating the pathology caused by <it>T. congolense</it>. WGA and PCR allowed a more comprehensive analysis of field infections with the detection of infections below the threshold of microscopy, and provided indications of interactions between parasite species that would otherwise remain undetected. The study raises important questions about the epidemiology of trypanosome infection in relation to disease that require a full scale longitudinal analysis.</p

Transport and Deposition of Saharan Dust Observed from Satellite Images and Ground Measurements

Haboob occurrence strongly impacts the annual variability of airborne desert dust in North Africa. In fact, more dust is raised from erodible surfaces in the early summer (monsoon) season when deep convective storms are common but soil moisture and vegetation cover are low. On 27 June 2018, a large dust storm is initiated over North Africa associated with an intensive westward dust transport. Far away from emission sources, dust is transported over the Atlantic for the long distance. Dust plume is emitted by a strong surface wind and further becomes a type of haboob when it merges with the southwestward deep convective system in central Mali at 0200 UTC (27 June). We use satellite observations to describe and estimate the dust mass concentration during the event. Approximately 93% of emitted dust is removed the dry deposition from the atmosphere between sources (10°N–25°N; 1°W–8°E) and the African coast (6°N–21°N; 16°W–10°W). The convective cold pool has induced large economic and healthy damages, and death of animals in the northeastern side of Senegal. ERA5 reanalysis has shown that the convective mesoscale impacts strongly the climatological location of the Saharan heat low (SHL)