Activity

Cytochrome P450 2D (CYP2D) enzymes metabolize many addictive drugs, including methamphetamine. Variable CYP2D metabolism in the brain may alter CNS drug/metabolite concentrations, consequently affecting addiction liability and neuropsychiatric outcomes; components of these can be modeled by behavioral sensitization in rats.

To investigate the role of CYP2D in the brain in methamphetamine-induced behavioral sensitization, rats were pretreated centrally with a CYP2D irreversible inhibitor (or vehicle) 20 h prior to each of 7 daily methamphetamine (0.5 mg/kg subcutaneous) injections. In vivo brain microdialysis was used to assess brain drug and metabolite concentrations, and neurotransmitter release.

CYP2D inhibitor (versus vehicle) pretreatment enhanced methamphetamine-induced stereotypy response sensitization. CYP2D inhibitor pretreatment increased brain methamphetamine concentrations and decreased the brain p-hydroxylation metabolic ratio. With microdialysis conducted on days 1 and 7, CYP2D inhibitor prion, brain drug concentrations, and striatal dopamine and serotonin release. Moreover, day 1 methamphetamine-induced neurotransmitter release may be an important predictor of subsequent behavioral sensitization. This suggests the novel contribution of CYP2D in the brain to methamphetamine-induced behavioral sensitization and suggests that the wide variation in human brain CYP2D6 may contribute to differential methamphetamine responses and chronic effects.

Over the past decade, adolescent cigarette smoking has been declining. However, adolescent nicotine consumption via electronic cigarettes is rapidly gaining popularity. Earlier onset nicotine use is associated with increased risk of dependence. A bidirectional relationship between nicotine and stress exists; perceived stress is a predictor for nicotine use, and stress reduction is a commonly reported reason for using nicotine.

We assessed the prolonged impact of adolescent high-dose nicotine and/or footshock exposure on adult nicotine self-administration, anxiety-like behaviour, and hormonal responsivity.

During adolescence (postnatal day [P]28-56) male Sprague-Dawley rats were assigned to one of five groups saline (SALPRE 1 ml/kg, SC, every day), nicotine (NICPRE 1 mg/kg, SC, alternating daily with saline; 14 total nicotine injections), footshock (SHOCKPRE 8 of 0.5 s, 0.8 mA alternating sessions; saline every day), or combination nicotine and footshock (NIC+SHOCK concurrent and alternating daily with sing nicotine intake. Avenues toward reducing stress in adolescent nicotine users may provide opportunities to reduce vulnerability to adult nicotine consumption.The hip fracture rates in South Africa were used to create ethnic-specific FRAX® models to facilitate fracture risk assessment.

The aim of this study was to develop FRAX models to compute the 10-year probability of hip fracture and major osteoporotic fracture and assess their potential clinical application.

Age- and sex-specific incidence of hip fracture and national mortality rates were incorporated into a FRAX model for the White, Black African, Coloured and Indian population of South Africa. Age-specific 10-year probabilities of a major osteoporotic fracture were calculated in women to determine fracture probabilities at a femoral neck T score of -2.5 SD, or those equivalent to a woman with a prior fragility fracture. Fracture probabilities were compared with those from selected countries.

Probabilities were consistently higher in Indian than in Coloured men and women, in turn, higher than in Black South Africans. For White South Africans, probabilities were lower than in Indians at young ages up to the age of about 80 years. When a BMD T score of -2.5 SD was used as an intervention threshold, FRAX probabilities in women age 50 years were approximately 2-fold higher than in women of the same age but with an average BMD and no risk factors. The increment in risk associated with the BMD threshold decreased progressively with age such that, at the age of 80 years or more, a T score of -2.5 SD was no longer a risk factor. Probabilities equivalent to women with a previous fracture rose with age and identified women at increased risk at all ages.

These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.

These FRAX models should enhance accuracy of determining fracture probability amongst the South African population and help guide decisions about treatment.Cryptosporidium is an important intestinal protozoan parasite that causes diarrhoea in humans and animals. To rapidly and specifically detect Cryptosporidium spp., we designed a pair of primers based on the small subunit ribosomal RNA (SSU rRNA) gene of Cryptosporidium spp. to be used in a new nanoparticle-assisted PCR (nano-PCR) assay. SGI-110 purchase The minimum detectable concentration (1.02 pg) of this nano-PCR was 10 times more sensitive than conventional PCR using the same primer pair. The DNA samples of C. parvum, C. baileyi, C. xiaoi, C. ryanae, and C. andersoni were successfully detected by the nano-PCR. No amplifications were evident with DNA samples of some common intestinal pathogens, including Eimeria tenella, Blastocystis sp., Giardia lamblia, Enterocytozoon bieneusi, and Balantidium coli. To validate the clinical usefulness of the novel nano-PCR, a total of 40 faecal samples from goats, camels, calves, and chickens were examined. The positive rate of Cryptosporidium spp. was 27.5% (11/40), which was consistent with that of an established nested PCR. These results indicate that the novel nano-PCR assay enables the rapid, specific, and accurate detection of Cryptosporidium infection in animals. The findings provide a technical basis for the clinical diagnosis, prevention, and control of cryptosporidiosis.Anisakiasis is an underrecognized condition globally, and accurate diagnosis remains problematic even in countries where the condition is well known. Our “systematic review” was conducted according to Prisma guidelines. The stated basis of our study was “syndromic surveillance.” Both methods are recognized in published literature as valid to identify or predict disease and to make accessible large amounts of evidence from published literature. Our study identified Anisakis allergy “hot spots” and other geographical areas where fish are highly infected with Anisakis without commensurate studies of human allergy. Results of our study will open up new lines of enquiry. Norway, used as an example to discredit the scientific integrity of our article, has a cuisine thriving with raw fish dishes and many sushi restaurants. The peer reviewed data sets, confirmed A. simplex sensitization among the Norwegian population, although this has been overlooked by the authors of the “Letter to the Editor.” The identification of hot spots in our study may be influential in many ways not the least in raising diagnostic suspicion to expedite accurate diagnosis.