Molecular epidemiology of malaria in Cameroon. XVIII. Polymorphisms of the Plasmodium falciparum merozoite surface antigen-2 gene in isolates from symptomatic patients

Merozoite surface antigen-2 (MSA-2) is a polymorphic genetic marker that is highly discriminatory for characterizing Plasmodium falciparum field isolates. Genetic diversity of isolates obtained from symptomatic patients residing in Yaounde, Cameroon was analyzed by an allele-specific polymerase chain reaction and direct sequencing of amplification products. Of 137 isolates, 25 (18%) had only FC27-type alleles, 40 (29%) had only 3D7-type alleles, and 72 (53%) had multiple parasite populations with both alleles. Of 295 fragments, 145 (49.2%) and 150 (50.8%) belonged to FC27 and 3D7 alleles, respectively. There were 23 different MSA-2 alleles (10 FC27-type and 13 3D7-type that yielded 44 different combinations in multiple infections). DNA sequencing showed distinct individual sequences. Sequences belonging to the FC27 allelic family were relatively conserved, with most of the polymorphism arising from differences in the number of repeat units. In contrast, the sequences within the GSA-rich region in 3D7 allelic family were less conserved, but many of the sequences in Cameroonian isolates have been identified in other isolates from geographically distant origins. Our results show an extensive diversity of the central region of MSA-2 in size, allelic family, combinations of these two features in multiple infections, and sequence variations underlying the complex population structure of P. falciparum clinical isolates in Yaounde, Cameroon.     

Neurosteroids: Expression of Functional 3β-Hydroxysteroid Dehydrogenase by Rat Sensory Neurons and Schwann Cells

Steroids which are synthesized within the nervous system, such as progesterone, have been termed 'neurosteroids'. Levels of progesterone are much larger in peripheral nerves of rats and mice than in plasma, and persist after removal of the steroidogenic endocrine glands. Schwann cells are a source of progesterone: when isolated from embryonic dorsal root ganglia, they can synthesize progesterone from pregnenolone, the obligate precursor of all steroids. Locally produced progesterone has been shown to play an important role in myelination of peripheral nerve. We show here that sensory neurons from embryonic dorsal root ganglia also express 3β-hydroxysteroid dehydrogenase and can convert [³H]pregnenolone to [³H]progesterone. Moreover, when cultured under different conditions and incubated for 24 h in the presence of 100 nM [³H]pregnenolone, they produce 5–10 times more [³H]progesterone than Schwann cells. The conversion of pregnenolone to progesterone by neurons is further increased by a diffusible factor produced by Schwann cells. Sensory neurons can also metabolize progesterone to 5α-dihydroprogesterone, but unlike Schwann cells, they do not produce 3α,5α-tetrahydroprogesterone, a potent positive allosteric modulator of γ-aminobutyric acid type A receptors. We also show that cells isolated from the adult nervous system still have the capacity to convert [³H]pregnenolone to progesterone and its 5α-reduced metabolites: neurons and Schwann cells purified from dorsal root ganglia of 6 week old male rats show a similar pattern of pregnenolone metabolism to cells isolated from 18 day old embryos. These findings further support the important role of progesterone in the development and regeneration of the peripheral nervous system.     

Genetic polymorphisms in IL‐2, IL‐10, TGF‐β1, and IL‐2RB and acute rejection in renal transplant patients

Acute rejection (AR) remains a concern for kidney transplantation. Cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. Single nucleotide polymorphisms (SNPs) in cytokines and their receptors may relate to AR. We investigated the relation between AR and SNPs in the genes encoding for IL‐2(–330G>T), IL‐10(?592C>A and ?1082G>A), TGF‐β1(915G>C), and IL‐2RB(rs228942 C>A and rs228953 C>T) in 325 renal transplant patients during the first year after transplantation. The overall incidence of AR was 15.4%. In multivariate analysis, only the use of induction therapy was correlated with AR (odds ratio 1.9; 95% confidence interval 1.1–3.7; p = 0.04). No statistically significant associations between the SNPs studied and AR were observed. SNPs in the investigated cytokines and their receptors were not associated with the risk of AR. Genotyping patients for these SNPs is unlikely to aid the clinician in adjusting the immunosuppressive therapy for individual patients.     

Cognitive Function in Older Patients with Postherpetic Neuralgia

Background and aims

Neuropathic pain has been shown to be accompanied by cognitive impairment, but the specific impact of postherpetic neuropathic pain on cognitive processes has not been explored. This study aims to evaluate the impact of pain on several domains of cognition in older patients with postherpetic neuralgia (PHN).

Methods

This cross‐sectional study ( clinicaltrial.gov NCT 00989040) included 84 individuals after signature of informed consent. Participants: 42 patients with PHN and 42 healthy volunteers. Of the 42 PHN patients, 21 received systemic treatment (antidepressants, anticonvulsants, opiates) and 21 had topical treatment with the 5% lidocaine medicated plaster. All participants performed a panel of four cognitive tests: reaction time, semantic memory, decision‐making, and visual memory (Cantab^®, Cambridge).

Results

Forty men and 44 women with a mean age of 72 ± 8 years participated. Each PHN patient was matched by age and gender with a healthy volunteer. Vigilance, decision‐making, and semantic memory were significantly impaired (P < 0.05) in patients on systemic treatment, especially with antidepressants, while no significant changes were noted between the lidocaine plaster group and their matched controls of healthy volunteers.

Conclusion

This study shows the deleterious effect of systemic PHN treatment on several domains of cognition. Cognitive impairment associated with pain and antidepressants may be reversed by topical pain management. Topical treatment with 5% lidocaine medicated plaster is a valuable alternative for pain alleviation and maintains cognitive integrity in this vulnerable population.