Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomised clinical trial

Objective: To compare the clinical efficacy and safety of rectal dihydroartemisinin (DATM- Cotecxin) and intravenous quinine in the treatment of severe malaria in children and adults.Setting: Moi Teaching and Referral Hospital, Eldoret, Kenya between July and November1998.Patients: A total of sixty seven patients aged two to sixty years with severe malaria were studied.Design: This was an open randomised comparative clinical trial.Outcome measures: These were parasite clearance time, fever clearance time, efficacy and the side effect profile of the two drugs.Results: The two groups were comparable on admission on the clinical and laboratory parameters. The parasite clearance time was shorter in the rectal DATM group than quinine group. There was no statistical difference on the fever clearance time and cure rates in thetwo groups. The adverse reaction profile was better with rectal DATM than with quinine, tinnitus observed more in the quinine group.Conclusion: Rectal DATM is faster in parasite clearance than quinine and is a safe and convenient alternative to quinine in the treatment of severe malaria

Sustained release formulation of an anti-tuberculosis drug based on para-amino salicylic acid-zinc layered hydroxide nanocomposite

Background: Tuberculosis (TB), is caused by the bacteria, Mycobacterium tuberculosis and its a threat to humans since centuries. Depending on the type of TB, its treatment can last for 6-24 months which is a major cause for patients non-compliance and treatment failure. Many adverse effects are associated with the currently available TB medicines, and there has been no new anti-tuberculosis drug on the market for more than 50 year, as the drug development is very lengthy and budget consuming process.Development of the biocompatible nano drug delivery systems with the ability to minimize the side effects of the drugs, protection of the drug from enzymatic degradation. And most importantly the drug delivery systems which can deliver the drug at target site would increase the therapeutic efficacy. Nanovehicles with their tendency to release the drug in a sustained manner would result in the bioavalibilty of the drugs in the body for a longer period of time and this would reduce the dosing frequency in drug administration. The biocompatible nanovehicles with the properties like sustained release of drug of the target site, protection of the drug from physio-chemical degradation, reduction in dosing frequency, and prolong bioavailability of drug in the body would result in the shortening of the treatment duration. All of these factors would improve the patient compliance with chemotherapy of TB.Result: An anti-tuberculosis drug, 4-amino salicylic acid (4-ASA) was successfully intercalated into the interlamellae of zinc layered hydroxide (ZLH) via direct reaction with zinc oxide suspension. The X-ray diffraction patterns and FTIR analyses indicate that the molecule was successfully intercalated into the ZLH interlayer space with an average basal spacing of 24 Å. Furthermore, TGA and DTG results show that the drug 4-ASA is stabilized in the interlayers by electrostatic interaction. The release of 4-ASA from the nanocomposite was found to be in a sustained manner. The nanocomposite treated with normal 3T3 cells shows it reduces cell viability in a dose- and time-dependent manner.Conclusions: Sustained release formulation of the nanocomposite, 4-ASA intercalated into zinc layered hydroxides, with its ease of preparation, sustained release of the active and less-toxic to the cell is a step forward for a more patient-friendly chemotherapy of Tuberculosis

Expanded geographic distribution and dietary strategies of the earliest Oldowan hominins and Paranthropus

The oldest Oldowan tool sites, ca. 2.6 million years ago (Ma), have previously been confined to Ethiopia’s Afar Triangle. We describe sites at Nyayanga, Kenya, dated to 3.032-2.581 Ma, and expand this distribution by over 1300 km. Furthermore, we found two hippopotamid butchery sites associated with mosaic vegetation and a C4 grazer-dominated fauna. Tool flaking proficiency was comparable to younger Oldowan assemblages, but pounding activities were more common. Tool use-wear and bone damage indicate plant and animal tissue processing. Paranthropus sp. teeth, the first from southwestern Kenya, possessed carbon isotopic values indicative of a diet rich in C4 foods. We argue that the earliest Oldowan was more widespread than previously known, used to process diverse foods including megafauna, and associated with Paranthropus from its onset

Perinatal morbidity at the Moi teachingand referral in hospital, Eldoret

(East African Medical Journal 2001 78 (10): 544-549

Anharmonic perturbation of neutron-proton pairs by the unpaired neutrons in heavy finite nuclei

7-15The properties of a finite heavy nucleus in which the number of neutrons N is not equal to the number of protons Z, N > Z, have been studied. It is assumed that the core of the nucleus is composed of proton-neutron pairs and the excess neutrons constitute the surface region of the nucleus. The interaction between a neutron and a proton constituting the neutron-proton pair is assumed to be harmonic. The unpaired neutrons in the surface region are assumed to interact with the neutron–proton pairs in the core of the nucleus anharmonically. Many body perturbation theory has been used to calculate the total energy of the nucleus, and thereby, we have calculated the binding energy per nucleon, called the binding fraction, the specific heat and the transition temperature. Speculation, as to how the alpha, beta and gamma radiations are emitted by a heavy nucleus, is also presented

Evaluation of Re–Os geochronology and Os isotope fingerprinting of Late Cretaceous terrestrial oils in Taranaki Basin, New Zealand

The rhenium-osmium (Re–Os) isotope system has been applied to several marine and lacustrine petroleum systems worldwide, showing good potential for dating crude oils and correlating them to their source rocks. Here we explore the applicability of the Re–Os geochronometer and Os isotope fingerprinting to terrestrial oils by comparing the Re and Os systematics of Late Cretaceous terrestrial oils from Taranaki Basin, New Zealand, and their correlated coaly source rocks. Comparison is also made with selected Late Cretaceous–Paleocene marine oils and source rocks with varying levels of terrestrial organic matter input. The asphaltene fractions of nine genetically related terrestrial oils from the Maui, Maari-Manaia and Tui Area fields in offshore Taranaki Basin contain low concentrations of Re (0.18–0.45 ppb) and 192Os (1.3–12.7 ppt) comparable to their correlated Late Cretaceous coaly source rocks (Rakopi and North Cape formations; Re 0.19–0.37 ppb, 192Os 5.3–9.6 ppt). The Re and 192Os concentrations in these terrestrial oils are generally one to two orders of magnitude lower than those in marine-sourced oils from the Kora Field in offshore Taranaki Basin and surface seeps in East Coast Basin. The 187Re/188Os and 187Os/188Os ratios of the terrestrial oils failed to yield a precise Re–Os isochron age. We attribute this to: (1) insufficient homogenisation of oils with widely variable initial 187Os/188Os (Osi) values inherited from thick, coaly source rock intervals (up to about 2700 m) within the Maui sub-basin and northern Kahurangi Trough kitchens; (2) insufficient spread of 187Re/188Os values (only 275 units); (3) insufficient time since oil expulsion (modelled to be from approximately 10 Ma to the present day) for the evolution of an isochron; and (4) possible effects of water washing of the oil columns. Although all of the studied oils are water-washed to varying degrees, there is no definitive evidence that water washing has disturbed the Re–Os systematics. The Osi values for the studied terrestrial oils inherited at the modelled time of oil expulsion (approximately 10 Ma) display a wide range (0.47–1.14) and do not provide a unique fingerprint of their Late Cretaceous coaly source rock formations. Osmium isotope compositions therefore appear to have limited potential for broad oil-source rock correlation within the predominantly coal-sourced petroleum systems of Taranaki Basin. The Osi values may, however, provide useful distinction of the terrestrial oils emanating from the Kahurangi Trough (Tui Area oils) from those of the Maui sub-basin (Maui and Maari-Manaia oils) based on the significantly more radiogenic values of the Tui Area oils (0.84–1.14 compared with 0.47–0.65 from Maui and Maari-Manaia oils). Overall, this study has provided useful insights into the potential application of the Re–Os isotope system to terrestrial, coal-sourced petroleum systems

HIV-1 Integrase Inhibitory Effects of Major Compounds Present in CareVid™: An Anti-HIV Multi-Herbal Remedy

In our continued study on the anti-HIV activity of compounds present in CareVidTM, we report the HIV-1 integrase ((HIV-1 IN) inhibitory effects of pellitorine (1), oleuropein (2), magnoflorine (3), crotepoxide (4), ent-kaurane-16β,17-diol (5), crotocorylifuran (6), lupeol (7), betulin (8), and ellagic acid (9) in an in vitro enzyme assay, and in an in silico study. Ellagic acid, pellitorine, lupeol, and betulin showed an in vitro percentage inhibition against HIV-1 IN of 21.1%, 19.0%, 18.5%, and 16.8%, respectively, at a standard concentration of 25 μg/mL. However, from a pharmacokinetic perspective, ellagic acid has poor bioavailability, due to rapid elimination in metabolism in the gut microbiome. It was postulated that known gut catabolites of ellagic acid, urolithin A (10) and urolithin B (11) could be more promising candidates in exploring the anti-HIV activity of ellagic acid-rich medicinal species consumed orally. On the contrary, urolithin A and urolithin B demonstrated lower activity with comparison to ellagic acid. The binding affinity of compounds 1–9, urolithin A, and urolithin B against the catalytic domain of HIV-1 IN was also explored by in silico methods. Docking studies showed oleuropein as the best candidate, with a predicted energy of binding of ΔG −5.81 kcal/mol, while ellagic acid showed moderate predicted inhibition (ΔG −4.38 kcal/mol) caused by the interaction between the carbonyl and the key Mg2+ ion in the active site

HIV-1 Reverse Transcriptase Inhibition by Major Compounds in a Kenyan Multi-Herbal Composition (CareVid™): In Vitro and In Silico Contrast.

CareVid is a multi-herbal product used in southwest Kenya as an immune booster and health tonic and has been anecdotally described as improving the condition of HIV-positive patients. The product is made up of roots, barks and whole plant of 14 African medicinal plants: Acacia nilotica (L.) Willd. ex Delile (currently, Vachelia nilotica (L.) P.J.H Hurter & Mabb.), Adenia gummifera (Harv.) Harms, Anthocleista grandiflora Gilg, Asparagus africanus Lam., Bersama abyssinica Fresen., Clematis hirsuta Guill. & Perr., Croton macrostachyus Hochst. ex Delile, Clutia robusta Pax (accepted as Clutia kilimandscharica Engl.), Dovyalis abyssinica (A. Rich.) Warb, Ekebergia capensis Sparm., Periploca linearifolia Quart.-Dill. & A. Rich., Plantago palmata Hook.f., Prunus africana Hook.f. Kalkman and Rhamnus prinoides L’Her. The objective of this study was to determine the major chemical constituents of CareVid solvent extracts and screen them for in vitro and in silico activity against the HIV-1 reverse transcriptase enzyme. To achieve this, CareVid was separately extracted using CH2Cl2, MeOH, 80% EtOH in H2O, cold H2O, hot H2O and acidified H2O (pH 1.5–3.5). The extracts were analysed using HPLC–MS equipped with UV diode array detection. HIV-1 reverse transcriptase inhibition was performed in vitro and compared to in silico HIV-1 reverse transcriptase inhibition, with the latter carried out using MOE software, placing the docking on the hydrophobic pocket in the subdomain of p66, the NNRTI pocket. The MeOH and 80% EtOH extracts showed strong in vitro HIV-1 reverse transcriptase inhibition, with an EC50 of 7 μg·mL−1. The major components were identified as sucrose, citric acid, ellagic acid, catechin 3-hexoside, epicatechin 3-hexoside, procyanidin B, hesperetin O-rutinoside, pellitorine, mangiferin, isomangiferin, 4-O-coumaroulquinic acid, ellagic acid, ellagic acid O-pentoside, crotepoxide, oleuropein, magnoflorine, tremulacin and an isomer of dammarane tetrol. Ellagic acid and procyanidin B inhibited the HIV-1 reverse transcription process at 15 and 3.2 µg/mL−1, respectively. Docking studies did not agree with in vitro results because the best scoring ligand was crotepoxide (ΔG = −8.55 kcal/mol), followed by magnoflorine (ΔG = −8.39 kcal/mol). This study showed that CareVid has contrasting in vitro and in silico activity against HIV-1 reverse transcriptase. However, the strongest in vitro inhibitors were ellagic acid and procyanidin B