A Possible Correlation Between Growth-Factor Sensitivity and Response to Mitoxantrone Treatment in a Murine Myeloid Leukaemia (SA7HD) Cell Line

SA7 murine myeloid leukaemia cells usually respond to stimulation in vitro by WEHI-conditioned medium by displaying increased dose-dependent proliferation. However, at recurrence following in vivo treatment of the leukaemia with mitoxantrone, the leukaemia cells developed significant insensitivity (p - 0.04) to stimulation by WEHI-conditioned medium. This altered growth-factor sensitivity was detected when two different assays were used. The recurrent leukaemic cells were morphologically indistinguishable from untreated leukaemic cells, but in normal mice they regained sensitivity to growth factors after a single transplant. The recurrent leukaemic cells were significantly resistant to some concentrations of mitoxantrone in vitro (p = 0.012). The magnitude of this resistance was mainly a function of the dose of mitoxantrone used in the initial treatment of the leukaemia. These data suggest an association between growth-factor sensitivity and response to mitoxantrone treatment including the development of resistance in the SA7HD murine myeloid leukaemia cell line.     

Induction and characterization of heat shock proteins of Salmonella typhi and their reactivity with sera from patients with typhoid fever.

The heat shock protein (HSP) response of Salmonella typhi following exposure to elevated growth temperatures was studied. Three major proteins with molecular sizes of 58, 68, and 88 kDa were abundantly expressed when S. typhi cells were shifted from 37 to 45 degrees C and to 55 degrees C. These proteins were also constitutively expressed at 37 degrees C. Western blotting and immunoprecipitation studies with anti-HSP monoclonal antibodies revealed that the 58- and 68-kDa proteins were analogous to the GroEL and DnaK proteins, respectively, of Escherichia coli. These HSPs are also abundantly present in the outer membrane fraction of disrupted cells and, to a lesser extent, in the cytosol. Immunoblotting experiments with sera from patients with a culture-positive diagnosis of typhoid fever showed the presence of antibodies to these HSPs. Nine of twelve sera reacted with the 58-, 68-, and 88-kDa proteins, while three sera reacted only with the 68- and 88-kDa proteins. All 10 sera from healthy individuals showed no binding to these HSPs. In light of the well-documented roles of HSPs in the pathogenesis of microbial infections and as immunodominant antigens, these findings may be relevant for a better understanding of disease processes and for the future development of diagnostic and preventive strategies.     

Hypoglycaemic Activity of Nauclea Latifolia Sm. (Rubiaceae) in Experimental Animals

Aqueous, ethanolic and hexane extracts of the leaves of Nauclea latifolia (Rubiaceae) were assessed for their fasting blood glucose lowering effect in normoglycaemic and streptozotocin - diabetic rats. Wistar strain albino rats were given different doses of the extracts after 18 hrs fast and their blood glucose measured at 0,1,2,4 and 6 hours after treatment. The aqueous and ethanolic extracts significantly lowered the fasting blood glucose levels of the STZ-diabetic rats in a dose-dependent manner. The highest dose administered (400mg/kg) lowered the fasting blood glucose of the diabetic rats by 31.7% (aqueous) and 36.1% (ethanolic) extracts. The aqueous extract did not significantly lower the glucose levels of normoglycaemic rats (maximum 6.6%), nor was any significant decrease seen in the rats administered with the hexane (maximum of 4.0% for normoglycaemic and 2.4% for diabetics) extract. The hypoglycaemic and antihyperglycaemic potentials of the aqueous and ethanolic extracts were comparable to that of glibenclamide (1mg/kg).These results further support the traditional use of the plant in the treatment of diabetes mellitus.     

Molecular epidemiology of the RNA satellite of <Emphasis Type="Italic">Rice yellow mottle virus</Emphasis> in Africa

Summary. Satellite RNA was sought in 51 isolates of Rice yellow mottle virus (RYMV) representative of the geographical, molecular and pathogenic variability of the virus in Africa. Three-quarters of the isolates from cultivated rice and wild gramineaceous hosts supported a satellite RNA. The prevalence of RYMV isolates that were associated with a satellite differed among regions, being c. 100% in West and Central Africa and c. 36% in East Africa. The RYMV satellite showed a low diversity as only seven of the 220 sequenced positions were variable. One insertion also occurred after serial host passages of the satellite. Two forms of the satellite differed by six substitutions forming three base pairs in one branch of the predicted RNA secondary structure. There was no evidence of intermediates between these two forms, but double-infection occurred. Each form had a specific geographical distribution: one occurred in Central Africa, the other elsewhere in Africa. There was no relation between the occurrence or the forms of the satellite and the phylogeny of the helper virus. The satellite was not involved in symptom modulation or ability to break host-plant resistances to the disease.Received January 29, 2003; accepted April 12, 2003 Published online June 24, 2003     

Hybrid Approach to Estimation of Underreporting of Tuberculosis Case Notification in High-Burden Settings With Weak Surveillance Infrastructure: Design and Implementation of an Inventory Study

BackgroundThe greatest risk of infectious disease undernotification occurs in settings with limited capacity to detect it reliably. World Health Organization guidance on the measurement of misreporting is paradoxical, requiring robust, independent systems to assess surveillance rigor. Methods are needed to estimate undernotification in settings with incomplete, flawed, or weak surveillance systems. This study attempted to design a tuberculosis (TB) inventory study that balanced rigor with feasibility for high-need settings.ObjectiveThis study aims to design a hybrid TB inventory study for contexts without World Health Organization preconditions. We estimated the proportion of TB cases that were not reported to the Ministry of Health in 2015. The study sought to describe TB surveillance coverage and quality at different levels of TB care provision. Finally, we aimed to identify structural-, facility-, and provider-level barriers to notification and reasons for underreporting, nonreporting, and overreporting.MethodsRetrospective partial digitalization of paper-based surveillance and facility records preceded deterministic and probabilistic record linkage; a hybrid of health facilities and laboratory census with a stratified sampling of HFs with no capacity to notify leveraged a priori knowledge. Distinct extrapolation methods were applied to the sampled health facilities to estimate bacteriologically confirmed versus clinical TB. In-depth interviews and focus groups were used to identify causal factors responsible for undernotification and test the acceptability of remedies.ResultsThe hybrid approach proved viable and instructive. High-specificity verification of paper-based records in the field was efficient and had minimal errors. Limiting extrapolation to clinical cases improved precision. Probabilistic record linkage is computationally intensive, and the choice of software influences estimates. Record absence, decay, and overestimation of the private sector TB treatment behavior threaten validity, meriting mitigation. Data management demands were underestimated. Treatment success was modest in all sectors (R=37.9%–72.0%) and did not align with treatment success reported by the state (6665/8770, 75.99%). One-fifth of TB providers (36/178, 20%) were doubtful that the low volume of patients with TB treated in their facility merited mastery of the extensive TB notification forms and procedures.ConclusionsSubnational inventory studies can be rigorous, relevant, and efficient in countries that need them even in the absence of World Health Organization preconditions, if precautions are taken. The use of triangulation techniques, with minimal recourse to sampling and extrapolation, and the privileging of practical information needs of local decision makers yield reasonable misreporting estimates and viable policy recommendations.     

Anti-trypanosomal activity of African medicinal plants: A review update

Ethnopharmacological relevance

African trypanosomiasis is one of the neglected tropical diseases caused by different species of trypanosomes that affect both human and livestock with devastating consequences in the continent. Most of the affected populations commonly use traditional medicinal plants for the treatment of the disease. Consequently, this prompted ethnopharmacological research activities on the anti-trypanosomal activity of a number of these African medicinal plants in order to validate their ethnomedicinal use. Furthermore, such studies could lead to the identification of chemical leads for the development of newer anti-trypanosomal agents from those plants. This review aims to provide updated information on the ethnopharmacological evidence of African medicinal plants with anti-trypanosomal activity.

Methods

Literature was collected via electronic search (PubMed, Sciencedirect, Medline and Google Scholar) from published articles that report on the in vitro or in vivo anti-trypanosomal activity of plants that were collected from different parts of Africa.

Results

African medicinal plants investigated for in vitro and in vivo anti-trypanosomal activity from January 1993 to October 2013 are systematically compiled and all the in vivo studies are critically discussed. A total of 264 plant species belonging to 79 families were investigated for anti-trypanosomal activity. However, only 48 bioactive anti-trypanosomal compounds were successfully isolated in pure forms. Furthermore, some of the plants were investigated for possible ameliorative effects on the trypanosome-induced pathological changes out of which 18 plants were reported to be effective while a few others were not. In spite of interesting preclinical ethnopharmacological evidence for anti-trypanosomal activity, not a single African medicinal plant was investigated in a clinical study.

Conclusion

Several African medicinal plants have demonstrated promising anti-trypanosomal effects but the studies on the anti-trypanosomal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.     

Identification of HPV16's E6 gene in suspected cases of cervical lesions and docking Study of its L1 protein with active components of Echinacea purpurae

BackgroundHPV 16 is the primary etiologic agent of cervical cancer and the presence of L1 and E6 oncoproteins are largely responsible for its virulence. It was the objective of this study to identify HPV16 isolates from suspected cases of cervical cancer at Specialist Hospital Sokoto and Sir Yahaya Memorail Hospiatal Birnin Kebbi, Nigeria and also to identify potent HPV16''s L1 protein inhibitor using in silico analysis.MethodsA total of 144 cervical samples consisting of 21 low grade squamous intraepithelial lesion, 6 high grade lesion and 117 negative pap smears were collected. The samples were subjected for molecular detection using PCR targeting E6 gene of the virus. Data generated for the molecular prevalence was statistically analyzed using Chi-square method. AutoDock Vina was used to carry out the molecular docking between 2hr5 and Chicoric acid, curcumin and Echinacoside.ResultsOut of the 144 samples, 24 samples were positive for the PCR representing 16.9% molecular prevalence rate. There is statistically significant association between cyto-diagnoses and presence of HPV16 (P < 0.05). Docking analysis showed that the Chicoric acid components of Echinacea purpurae have strong binding affinity (-8.7 kcal/mol) to the L1 protein of the HPV.ConclusionThis study provides data on HPV 16 epidemiology in northern Nigeria, and also provides novel evidence for consideration on certain interacting residues, when synthesizing Anti-HPV compounds in the wet lab.     

Isolation,characterisation and complement fixation activity of acidic polysaccharides from Argemone mexicana used as antimalarials in Mali

ContextGlobal studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available.ObjectiveThis study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana.Materials and methodsAcidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses.ResultsThe monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while β-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH₅₀ value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL.Discussion and conclusionsPolysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents.