BACKGROUND: In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. METHODS: Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. RESULTS: Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. CONCLUSION: These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S.
BACKGROUND: Pre-eclampsia/eclampsia is one of the most common causes of maternal and perinatal morbidity and mortality in low and middle income countries. Magnesium sulfate is the drug of choice for prevention of seizures as part of comprehensive management of the disease. Despite the compelling evidence for the effectiveness of magnesium sulfate, concern has been expressed about its safety and potential for toxicity, particularly among providers in low- and middle-income countries. The purpose of this review was to determine whether the literature published in these global settings supports the concerns about the safety of use of magnesium sulfate. METHODS: An integrative review of the literature was conducted to document the known incidences of severe adverse reactions to magnesium sulphate, and specific outcomes of interest related to its use. All types of prospective clinical studies were included if magnesium sulfate was used to manage pre-eclampsia or eclampsia, the study was conducted in a low- or middle-income country, and the study included the recording of the incidence of any adverse side effect resulting from magnesium sulfate use. RESULTS: A total of 24 studies that compared a magnesium sulfate regimen against other drug regimens and examined side effects among 34 subject groups were included. The overall rate of absent patellar reflex among all 9556 aggregated women was 1.6%, with a range of 0-57%. The overall rate of respiratory depression in 25 subject groups in which this outcome was reported was 1.3%, with a range of 0–8.2%. Delay in repeat administration of magnesium sulfate occurred in 3.6% of cases, with a range of 0-65%. Calcium gluconate was administered at an overall rate of less than 0.2%. There was only one maternal death that was attributed by the study authors to the use of magnesium sulfate among the 9556 women in the 24 studies. CONCLUSION: Concerns about safety and toxicity from the use of magnesium sulfate should be mitigated by findings from this integrative review, which indicates a low incidence of the most severe side effects, documented in studies that used a wide variety of standard and modified drug regimens. Adverse effects of concern to providers occur infrequently, and when they occurred, a delay of repeat administration was generally sufficient to mitigate the effect. Early screening and diagnosis of the disease, appropriate treatment with proven drugs, and reasonable vigilance for women under treatment should be adopted as global policy and practice.
An evaluation was made of the effects of seven neurotoxic insecticides (esfenvalerate, indoxacarb, clothianidin, thiacloprid, azinphosmethyl, phosmet and imidacloprid), one insect growth regulator (novaluron) and two fungicides (myclobutanin and mancozeb), with water as the control, on the horizontal mobility of plum curculios exposed to dried pesticide residues. Mobility was recorded over a 2 h period using ethological tracking software. Mortality was recorded immediately after horizontal mobility experiments and 24 h later.
In this work we investigated the formation, reactivity and anti-platelet activity of various mixed disulfide conjugates of clopidogrel. Our results showed that the production of the active metabolite (AM) from 2-oxoclopidogrel by human liver microsomes (HLMs) is greatly affected by the thiol reductants used. Among the ten thiol compounds tested, glutathione (GSH) is most efficient in producing the AM at a rate of 167 pmoles AM/min/mg HLM. Interestingly, no AM but only the mixed disulfide conjugates were formed in the presence of 6-chloropyridazine-3-thiol (CPT), 2,5-dimethylfuran-3-thiol (DFT), and 3-nitropyridine-2-thiol (NPT). The MS and MS2 spectra of the conjugates of these thiol compounds confirmed the presence of a mixed disulfide bond linkage between the AM and the thiol reductants. Kinetic studies revealed that the mixed disulfide conjugates were capable of exchanging thiols with GSH to release the AM with second order rate constants ranging from 1.2 to 28 M(-1)s(-1). The mixed disulfide conjugates of CPT and NPT showed potent inhibition of platelet aggregation after pre-treatment with 1 mM GSH, confirming that the AM is responsible for the anti-platelet activity of clopidogrel. Collectively, our results provide strong support for a P450-mediated bioactivation mechanism involving the initial formation of a glutathionyl conjugate followed by thiol-disulfide exchange with another GSH molecule to release the AM. Furthermore, the stable mixed disulfide conjugates identified in this study provide a platform to quantitatively generate the therapeutic AM without the need for P450-mediated bioactivation. This property can be further explored in order to overcome the inter-individual variability in clopidogrel therapy.
Carbendazim (MBC) (methyl-2-benzimidazole carbamate) and tebuconazole (TBZ) ((RS)-1-(4-chlorophenyl)-4,4-dimethyl-3-(1H-1,2,4-triazol-1-ylmethyl)pentan-3-ol) are widely used in agriculture for the prevention and control of fungal diseases. Solid lipid nanoparticles and polymeric nanocapsules are carrier systems that offer advantages including changes in the release profiles of bioactive compounds and their transfer to the site of action, reduced losses due to leaching or degradation, and decreased toxicity in the environment and humans. The objective of this study was to prepare these two types of nanoparticle as carrier systems for a combination of TBZ and MBC, and then investigate the release profiles of the fungicides as well as the stabilities and cytotoxicities of the formulations. Both nanoparticle systems presented high association efficiency (>99%), indicating good interaction between the fungicides and the nanoparticles. The release profiles of MBC and TBZ were modified when the compounds were loaded in the nanoparticles, and cytotoxicity assays showed that encapsulation of the fungicides decreased their toxicity. These fungicide systems offer new options for the treatment and prevention of fungal diseases in plants.
Vasectomy is currently the only long-acting contraceptive option available for men, despite increasing demand and potentially significant positive impacts on human health of additional male contraceptive options. Vasalgel ™ is a high molecular weight hydrogel polymer being developed as a non-hormonal long-acting reversible male contraceptive. Vasalgel consists of styrene-alt-maleic acid dissolved in dimethyl sulfoxide, which is distinct from styrene-alt-maleic anhydride materials previously studied.
Severe haze is a major public health concern in China and India. Both countries rely heavily on coal for energy, and sulfur dioxide (SO2) emitted from coal-fired power plants and industry is a major pollutant contributing to their air quality problems. Timely, accurate information on SO2 sources is a required input to air quality models for pollution prediction and mitigation. However, such information has been difficult to obtain for these two countries, as fast-paced changes in economy and environmental regulations have often led to unforeseen emission changes. Here we use satellite observations to show that China and India are on opposite trajectories for sulfurous pollution. Since 2007, emissions in China have declined by 75% while those in India have increased by 50%. With these changes, India is now surpassing China as the world’s largest emitter of anthropogenic SO2. This finding, not predicted by emission scenarios, suggests effective SO2 control in China and lack thereof in India. Despite this, haze remains severe in China, indicating the importance of reducing emissions of other pollutants. In India, ~33 million people now live in areas with substantial SO2 pollution. Continued growth in emissions will adversely affect more people and further exacerbate morbidity and mortality.
Large Hesperian-aged (~3.7 Ga) layered deposits of sulfate-rich sediments in the equatorial regions of Mars have been suggested to be evidence for ephemeral playa environments. But early Mars may not have been warm enough to support conditions similar to what occurs in arid environments on Earth. Instead cold, icy environments may have been widespread. Under cryogenic conditions sulfate formation might be blocked, since kinetics of silicate weathering are typically strongly retarded at temperatures well below 0 °C. But cryo-concentration of acidic solutions may counteract the slow kinetics. Here we show that cryo-concentrated acidic brines rapidly chemically weather olivine minerals and form sulfate minerals at temperatures as low as -60 °C. These experimental results demonstrate the viability of sulfate formation under current Martian conditions, even in the polar regions. An ice-hosted sedimentation and weathering model may provide a compelling description of the origin of large Hesperian-aged layered sulfate deposits on Mars.
The roots of the “shy plant” Mimosa pudica L. emit a cocktail of small organic and inorganic sulfur compounds into the environment, including SO2, methylsulfinic acid, pyruvic acid, lactic acid, ethanesulfinic acid, propane sulfinic acid, 2-mercaptoaniline, S-propyl propane 1-thiosulfinate, and thioformaldehyde, an elusive and highly unstable compound never before reported to be emitted by a plant. When soil around the roots is dislodged or when seedling roots are touched, an odor is detected. The perceived odor corresponds to emission of higher amounts of propanesulfenic acid, 2-mercaptoaniline, S-propyl propane 1-thiosulfinate, and phenothiazine. The mechanosensitivity response is selective. Whereas touching the roots with soil or human skin resulted in odor detection, agitating the roots with other materials such as glass did not induce a similar response. Light and electron microscopy studies revealed the presence of microscopic sac-like root protuberances. Elemental analysis of these hairs by energy dispersive X-ray spectroscopy revealed them to contain higher levels of K+ and Cl- compared to the surrounding tissue. Exposing the hairs to stimuli that caused in odor emission resulted in a reduction in the levels of K+ and Cl- in the touched area. The mechanistic implications of the variety of sulfur compounds observed vis-à-vis the pathways for their formation are discussed.
Chimpanzees of the Sonso community, Budongo Forest, Uganda were observed eating clay and drinking clay-water from waterholes. We show that clay, clay-rich water, and clay obtained with leaf sponges, provide a range of minerals in different concentrations. The presence of aluminium in the clay consumed indicates that it takes the form of kaolinite. We discuss the contribution of clay geophagy to the mineral intake of the Sonso chimpanzees and show that clay eaten using leaf sponges is particularly rich in minerals. We show that termite mound soil, also regularly consumed, is rich in minerals. We discuss the frequency of clay and termite soil geophagy in the context of the disappearance from Budongo Forest of a formerly rich source of minerals, the decaying pith of Raphia farinifera palms.