Biocompatible Germanium-Doped Hydroxyapatite Nanoparticles for Promoting Osteogenic Differentiation and Antimicrobial Activity

Hydroxyapatite (HAp) has been the main protagonist in the quest for an ideal biomaterial for regenerative medicine over the last half a century. To control its properties, this material has commonly been doped with chemical elements other than its natural stoichiometric constituents: Ca, O, P, and H. Here, we report on the first analysis of the biological response to germanium-doped hydroxyapatite (Ge-HAp). Cytotoxicity, osteogenic differentiation induction, and colony formation potential were measured on dental pulp stem cells, while the antimicrobial effect was assessed against Gram-negative Escherichia coli, Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. All analyses were run in comparison to Ge-free HAp. Cell viability was inversely dependent on the nanoparticle concentration and incubation time. Adding Ge to HAp reduced cell viability relative to HAp after 24–72 h incubation periods, but the effect was reversed after longer incubations, when the viability of cells treated with low doses of Ge-HAp exceeded that of HAp-treated cells and became comparable with control culture. Both HAp and Ge-HAp induced mineral formation in the cell culture, but the effect was more pronounced for Ge-HAp. Likewise, relative to both control cells and cells exposed to HAp, Ge-HAp upregulated the expression of all three osteogenic markers analyzed, namely, alkaline phosphatase, RUNX2, and osteocalcin, exerting the key influence on osteogenesis in its early, differentiation stage. The colony formation capacity of stem cells, however, was impaired by HAp and even more so by Ge-HAp. The antimicrobial effect was dependent on the microorganisms tested. Thus, whereas the antimicrobial activity was absent against E. coli, it was evident against MRSA and C. albicans. While the antibacterial activity against MRSA was weakened by the addition of Ge to HAp, the antimycotic activity against C. albicans was intensified with the addition of Ge. These findings demonstrate a significant potential of Ge-doped HAp nanoparticles in regenerative medicine due to their pronounced biocompatibility, osteoinductivity, and antimicrobial activity

Molecular typing reveals substantial Plasmodium vivax infection in asymptomatic adults in a rural area of Cameroon

BACKGROUND: Malaria in Cameroon is due to infections by Plasmodium falciparum and, to a lesser extent, Plasmodium malariae and Plasmodium ovale, but rarely Plasmodium vivax. A recent report suggested “Plasmodium vivax–like” infections around the study area that remained unconfirmed. Therefore, molecular and antigenic typing was used to investigate the prevalence of P. vivax and Duffy in asymptomatic adults resident in Bolifamba. METHODS: A cross-sectional study was conducted from July 2008 to October 2009. The status of all parasite species was determined by nested PCR in 269 blood samples collected. The P. falciparum and P. vivax anti-MSP/CSP antibody status of each subject was also determined qualitatively by a rapid card assay. Parasite DNA was extracted from a sample infected with three parasite species, purified and sequenced. The Duffy antigen status of 12 subjects infected with P. vivax was also determined by sequencing. In silico web-based tools were used to analyse sequence data for similarities and matches to reference sequences in public DNA databases. RESULTS: The overall malaria parasite prevalence in 269 individuals was 32.3% (87) as determined by PCR. Remarkably, 14.9% (13/87) of infections were caused either exclusively or concomitantly by P. vivax, established both by PCR and microscopic examination of blood smears, in individuals both positive (50%, 6/12) and negative (50%, 6/12) for the Duffy receptor. A triple infection by P. falciparum, P. vivax and P. malariae, was detected in one infected individual. Anti-MSP/CSP antibodies were detected in 72.1% (194/269) of samples, indicating high and continuous exposure to infection through mosquito bites. DISCUSSION: These data provide the first molecular evidence of P. vivax in Duffy positive and negative Cameroonians and suggest that there may be a significant prevalence of P. vivax infection than expected in the study area. Whether the P. vivax cases were imported or due to expansion of a founder effect was not investigated. Notwithstanding, the presence of P. vivax may complicate control efforts if these parasites become hypnozoitic or latent as the liver stage. CONCLUSIONS: These data strongly suggest that P. vivax is endemic to the south-west region of Cameroon and should be taken into account when designing malaria control strategies

The role of UV and blue light in photo-eradication of microorganisms

Abstract: Photo-eradication of microorganisms with UV and blue light has been around since the 1870s. Research to further the development and deployment of germicidal UV and violet-blue light has been on the rise since COVID-19 pandemic. This paper traces the evolution of UV and violet-blue light, presents suggested ways to exploit two leading germicidal light technologies—far UV and pulsed blue light (PBL)—in the ongoing quest to effectively stem the spread of pandemic diseases. An effective way to overcome or minimize the spread of disease is to inactivate and reduce the number of viral particles both in the environment and in accessible parts of patients. This can be achieved by irradiating spaces, infected air, and the general environment with PBL or far UV, and by similarly disinfecting supplies, tools, and equipment. Irradiating the oronasal cavity of infected patients with PBL could clear the virus and kill oral opportunistic bacteria that worsen coronavirus infections. The advantages and disadvantages of the two-leading photo-disinfection light technologies are discussed

Review of the comparative susceptibility of microbial species to photoinactivation using 380-480 nm violet-blue light

Antimicrobial violet-blue light is an emerging technology designed for enhanced clinical decontamination and treatment applications, due to its safety, efficacy and ease of use. This systematised review was designed to compile the current knowledge on the antimicrobial efficacy of 380-480 nm light on a range of healthcare and food related pathogens including vegetative bacteria, bacterial endospores, fungi and viruses. Data was compiled from 79 studies, with the majority focussing on wavelengths in the region of 405 nm. Analysis indicated that Gram positive and negative vegetative bacteria are the most susceptible organisms, whilst bacterial endospores, viruses and bacteriophage are the least. Evaluation of the dose required for a 1 log10 reduction of key bacteria compared to population, irradiance and wavelength indicated that microbial titre and light intensity had little effect on the dose of 405 nm light required, however linear analysis indicated organisms exposed to longer wavelengths of violet-blue light, may require greater doses for inactivation. Additional research is required to ensure this technology can be used effectively, including: investigating inactivation of multidrug-resistant organisms, fungi, viruses and protozoa; further knowledge about the photodynamic inactivation mechanism of action; the potential for microbial resistance; and the establishment of a standardised exposure methodology

Treatment of Wilson's disease with zinc. XVII: Treatment during pregnancy

Therapy of Wilson's disease continues to evolve. In 1997, zinc acetate was added to the list of drugs approved by the Food and Drug Administration, which includes penicillamine and trientine. The mechanism of zinc's anticopper action is unique. It induces intestinal cell metallothionein, which binds copper and prevents its transfer into blood. As intestinal cells die and slough, the contained copper is eliminated in the stool. Thus, zinc prevents the intestinal absorption of copper. It is universally agreed that pregnant Wilson's disease patients should remain on anticopper therapy during pregnancy. There are numerous reports of such patients stopping penicillamine therapy to protect their fetus from teratogenicity, only to undergo serious deterioration and even death from renewed copper toxicity. Penicillamine and trientine have teratogenic effects in animals, and penicillamine has known teratogenic effects in humans. In this report we discuss the results of 26 pregnancies in 19 women who were on zinc therapy throughout their pregnancy. The evidence is good that zinc protects the health of the mother during pregnancy. Fetal outcomes were generally quite good, although one baby had a surgically correctable heart defect and one had microcephaly.(Hepatology 2000;31:364-370.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34776/1/510310216_ftp.pd

Toxicological studies of the stem bark extract of Khaya grandifoliola in rats

Khaya grandifoliola (Welw) CDC (Meliaceae) is a tropical medicinal plant widely used in Africa for the management of malaria. In this study, toxicological evaluation of the aqueous extract of the stem bark of the plant has been evaluated with a view to ascertaining some of its possible toxic effects in the rats. Healthy rats of both sexes weighing between 62 g - 69 g body weight were used for this study. A group of rats were administered with graded doses (100, 200 and 500 mg/kg body weight, o.p) of the extract daily for 21 days. At the end of the 7 days, 21 days treatment periods and 21 days post-treatment (Recovery) period, the different groups of animals were sacrificed and assessed for tissue damage by measuring the plasma, liver, heart and spleen activities of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP). The liver, kidney, heart and spleen were also subjected to histopathological assessment. The result showed that following 1 week of administration of the extract that there was significant (p < 0.05) in the activities of plasma AST, ALT, and a decrease in plasma ALP, liver AST and ALT when compared to control. However, following 21 post-treatment days, these changes in enzyme activities were not significantly different (p < 0.05) from control values. There were also no marked histopathological alterations in any of the organs for different treatment groups except for the 500 mg/kg body weight group that showed mild lesions in the liver, kidney and spleen. In conclusion, administration of the extract depressed the liver amino transferase activities in a dose-dependent manner, with concurrent increased patternsof activity in the plasma. This indicates that K. grandifoliola extract could be toxic when administered chronically at high doses.Keywords: ALP, AST, ALT, Heart, Histology, Kidney, Liver, Spleen

Topical treatment with Copaifera langsdorffii oleoresin improves wound healing in rats

Copaifera langsdorffii oleoresin (copaiba) has been used in the Amazon as traditional wound healing remedy for centuries. Since its mechanisms of action remain unclear, we investigated its effects on excisional wounds in rats. Wounds were made on the dorsum of animals assigned to three groups: saline, control cream and 10% copaiba cream, and assessed on days 2, 7 and 14 post-wounding morphometrically, histologically and biochemically. Wound healing rate was faster in copaiba than in saline or cream groups. This was corroborated by matrix metalloproteinase (MMP)-2 activity which rose progressively throughout in copaiba group. MMP-9, a marker of inflammation, was not detectable at day 14 in copaiba group, but persisted in the other groups. Moreover, histology showed early population of copaiba-treated wounds by inflammatory cells, and by day 14 this group had less fibroblasts and more organized collagen. Further, copaiba group synthesized collagen faster than saline and cream groups, as evidenced by progressive increases in the amounts of hydroxyproline at days 7 and 14 (p &lt; 0.012). These findings suggest that 10% copaiba oleoresin cream promotes wound healing in rats by regulating MMP-2 and MMP-9 activities, stimulating collagen synthesis and promoting tissue remodeling and reepithelialization