The use of antibiotics during pregnancy: A cross-sectional study of knowledge, attitude, and practices among antenatal care attendees in Northern Ghana.

Background and aims: The promotion of rational use of antibiotics among pregnant women is eminent not only for the risk of teratogenicity in the developing fetus but also the risk of drug resistance with its concomitant high cost of health care. Studies on antibiotic self-medication among pregnant women in Northern Ghana are rare. Improving the knowledge and awareness among the vulnerable groups about the appropriate use of antibiotics can help in limiting the antibiotic resistance menace. We, therefore, conducted this study to assess the knowledge, attitude, and practice (KAP) toward antibiotic use among pregnant women attending an antenatal clinic at a primary health care in Tolon, Northern Region, Ghana. Method: We conducted a cross-sectional study using an interviewer-administered questionnaire to assess the KAP of 702 pregnant women on antibiotic use. This study was conducted in the Tolon Health Center (THC) from March 2021 and ended in October 2021. Results: In this study, 55.6% of pregnant women had good knowledge and 45.3% of them had engaged in self-medication with antibiotics while pregnant. There were statistically significant associations between participants' background and obstetric characteristics and knowledge of antibiotic use and antibiotic resistance, except for age, marital status, and parity. Also, there was a significant association between pregnant women's knowledge and self-medication or over-the-counter purchase of antibiotics. Conclusion: We concluded that higher education level, monthly income, good practice, and good knowledge were significantly associated with a reduced likelihood of self-medication with antibiotics. A well-structured education that could be easily accepted and understood by pregnant women on the risks of antibiotic self-medication should be included in the routine education at the antenatal clinics.

A Sustainable, Green-Processed, Ag-Nanoparticle-Incorporated Eggshell-Derived Biomaterial for Wound-Healing Applications.

The eggshell membrane (ESM) is a natural biomaterial with unique physical and mechanical properties that make it a promising candidate for wound-healing applications. However, the ESM's inherent properties can be enhanced through incorporation of silver nanoparticles (AgNPs), which have been shown to have antimicrobial properties. In this study, commercially produced AgNPs and green-processed AgNPs were incorporated into ESM and evaluated for their physical, biological, and antimicrobial properties for potential dermal application. The ESM was extracted using various techniques, and then treated with either commercially produced AgNPs (Sigma-Aldrich, Poole, UK) or green-synthesized AgNPs (Metalchemy, London, UK) to produce AgNPs-ESM samples. The physical characteristics of the samples were evaluated using scanning electron microscopy (SEM), Fourier Transform Infrared (FTIR) spectroscopy, and the biological properties were assessed through in vitro studies using human dermal fibroblasts (HDFs) and BJ cells. The SEM analysis of the AgNPs-ESM samples showed localization of AgNPs on the ESM surface, and that the ESM maintained its structural integrity following AgNP incorporation. The FTIR confirmed loading of AgNPs to ESM samples. The biological studies showed that the 5 µg/mL AgNPs-ESM samples were highly biocompatible with both HDFs and BJ cells, and had good viability and proliferation rates. Additionally, the AgNPs-ESM samples demonstrated pro-angiogenic properties in the CAM assay, indicating their potential for promoting new blood vessel growth. Assessment of the antimicrobial activity of the enhanced AgNPs/ESMs was validated using the International Standard ISO 16869:2008 methodology and exploited Cladosporium, which is one of the most commonly identified fungi in wounds, as the test microorganism (≥5 × 106 cells/mL). The AgNPs-ESM samples displayed promising antimicrobial efficacy as evidenced by the measured zone of inhibition. Notably, the green-synthesized AgNPs demonstrated greater zones of inhibition (~17 times larger) compared to commercially available AgNPs (Sigma-Aldrich). Although both types of AgNP exhibited long-term stability, the Metalchemy-modified samples demonstrated a slightly stronger inhibitory effect. Overall, the AgNPs-ESM samples developed in this study exhibited desirable physical, biological, and antimicrobial properties for potential dermal wound-dressing applications. The use of green-processed AgNPs in the fabrication of the AgNPs-ESM samples highlights the potential for sustainable and environmentally friendly wound-healing therapies. Further research is required to assess the long-term biocompatibility and effectiveness of these biomaterials in vivo.

A drug-incorporated-microparticle-eggshell-membrane-scaffold (DIMES) dressing: A novel biomaterial for localised wound regeneration.

Chronic wounds affect millions of people annually and have emotional and financial implications in addition to health issues. The current treatment for chronic wounds involves the repeated use of bandages and drugs such as antibiotics over an extended period. A cost-effective and convenient solution for wound healing is the development of drug-incorporated bandages. This study aimed to develop a biocompatible bandage made of drug-incorporated poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) and eggshell membrane (ESM) for cornea wound healing. ESM has desirable properties for wound healing and can be isolated from eggshells using acetic acid or ethylenediaminetetraacetic acid (EDTA) protocols. Fluorescein isothiocyanate-labelled Bovine Serum Albumin (FITC-BSA) was used as a model drug, and the PLGA MPs were fabricated using a solvent extraction method. The MPs were successfully attached to the fibrous layer of the ESM using NaOH. The surface features of the ESM samples containing MPs were studied using a field emission scanning electron microscope (FESEM) and compared with blank ESM images. The findings indicated that the MPs were attached to the ESM fibres and had similar shapes and sizes as the control MPs. The fibre diameters of the MPs samples were assessed using Fiji-ImageJ software, and no significant changes were observed compared to the blank ESM. The surface roughness, Ra values, of the MPs incorporated ESM samples were evaluated and compared to the blank ESM, and no significant changes were found. Fourier transform infrared (FTIR) spectroscopy was used to analyse the chemical Composition of the bandage, and the spectra showed that the FBM were effectively incorporated into the ESM. The FTIR spectra identified the major peaks of the natural ESM and the PLGA polymer in the bandage. The bandage was transparent but had a reduced visibility in the waterproof test card method. The bandage achieved sustained drug release up to 10 days and was found to be biocompatible and non-toxic in a chorioallantoic membrane (CAM) assay. Overall, the drug-incorporated PLGA MPs-ESM bandage has great potential for treating chronic wounds.

The chicken eggshell membrane: a versatile, sustainable, biological material for translational biomedical applications.

Naturally derived materials are often preferred over synthetic materials for biomedical applications due to their innate biological characteristics, relative availability, sustainability, and agreement with conscientious end-users. The chicken eggshell membrane (ESM) is an abundant resource with a defined structural profile, chemical composition, and validated morphological and mechanical characteristics. These unique properties have not only allowed the ESM to be exploited within the food industry but has also led to it be considered for other novel translational applications such as tissue regeneration and replacement, wound healing and drug delivery. However, challenges still exist in order to enhance the native ESM (nESM): the need to improve its mechanical properties, the ability to combine/join fragments of ESM together, and the addition or incorporation of drugs/growth factors to advance its therapeutic capacity. This review article provides a succinct background to the nESM, its extraction, isolation, and consequent physical, mechanical and biological characterisation including possible approaches to enhancement. Moreover, it also highlights current applications of the ESM in regenerative medicine and hints at future novel applications in which this novel biomaterial could be exploited to beneficial use.

Exploring prostate cancer screening among men in Accra using the health belief model.

Objective: To explore the prevalence of prostate cancer screening among Ghanaian men and interrogate why some individuals screen for the disease and others do not. Design: A cross-sectional questionnaire survey based on the Health Belief Model was used to collect data from 356 men aged 40 years and above. Data were collected between February and March 2021. Setting: The study was conducted in the Accra metropolitan area of the Greater Accra region of Ghana. Participants: Convenience sampling was used to recruit participants for the study. Results: Although 86% of the respondents had heard about prostate cancer, only 23% had ever screened for it. Logistic regression analysis suggested that knowledge of the disease (OR = 1.19, CI 95% = 1.03 -1.38) and barriers to screening (OR = .87, CI 95% = .83 -.91) were statistically significant predictors of screening behaviour. Conclusion: HBM has limited predictive power as far as our study is concerned. We suggest increasing public education on prostate cancer and its screening methods. The cost of screening should also be made more affordable so as not to become a barrier. Funding: None declared.

Therapeutic Application of an Ag-Nanoparticle-PNIPAAm-Modified Eggshell Membrane Construct for Dermal Regeneration and Reconstruction.

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived extract, it demonstrates inherent biocompatibility/biodegradability. To further enhance its therapeutic and clinical potential, the ESM can be modified with the thermo-responsive polymer, poly(N-isopropylacrylAmide) (PNIPAAm) as well as the incorporation of (drug-loaded) silver nanoparticles (AgNP); essentially, by a simple change in temperature, the release and delivery of the NP can be targeted and controlled. In this study, ESM samples were isolated using a decellularization protocol, and the physical and mechanical characteristics were profiled using SEM, FT-IR, DSC and DMA. PNIPAAm was successfully grafted to the ESM via amidation reactions and confirmed using FT-IR, which demonstrated the distinctive peaks associated with Amide A (3275 cm−1), Amide B (2970 cm−1), Amide I (1630 cm−1), Amide II (1535 cm−1), CH2, CH3 groups, and Amide III (1250 cm−1) peaks. Confirmation of the incorporation of AgNP onto the stratified membrane was confirmed visually with SEM, qualitatively using FT-IR and also via changes in absorbance at 380 nm using UV-Vis spectrophotometry during a controlled release study for 72 h. The biocompatibility and cytotoxicity of the novel constructs were assessed using human dermal fibroblast (HDFa) and mouse dermal fibroblast (L929) cells and standard cell culture assays. Metabolic activity assessment (i.e., MTS assay), LDH-release profiles and Live/Dead staining demonstrated good attachment and spreading to the samples, and high cell viability following 3 days of culture. Interestingly, longer-term viability (>5 days), the ESM-PNIPAAm and ESM-PNIPAAm (AgNP) samples showed a greater and sustained cell viability profile. In summary, the modified and enhanced ESM constructs were successfully prepared and characterized in terms of their physical and mechanical profiles. AgNP were successfully loaded into the construct and demonstrated a desirable release profile dependent on temperature modulation. Fibroblasts cultured on the extracted ESM samples and ESM-PNIPAAm demonstrated high biocompatibility in terms of high cell attachment, spreading, viability and proliferation rates. As such, this work summarizes the development of an enhanced ESM-based construct which may be exploited as a clinical/therapeutic wound dressing as well as a possible application as a novel biomaterial scaffold for drug development.

The eggshell membrane: A potential biomaterial for corneal wound healing.

The eggshell membrane (ESM) is an abundant resource with innate complex structure and composition provided by nature. With at least 60 million tonnes of hen eggs produced globally per annum, utilisation of this waste resource is highly attractive in positively impacting sustainability worldwide. Given the morphology and mechanical properties of this membrane, it has great potential as a biomaterials for wound dressing. However, to date, no studies have demonstrated nor reported this application. As such, the objective of this investigation was to identify and optimise a reproducible extraction protocol of the ESM and to assess the physical, chemical, mechanical and biological properties of the substrate with a view to use as a wound dressing. ESM samples were isolated by either manual peeling (ESM-strip) or via extraction using acetic acid [ESM-A0.5] or ethylenediaminetetraacetic acid, EDTA [ESM-E0.9]. Energy dispersive X-ray spectroscopy (EDS) confirmed that there were no traces of calcium residues from the extraction process. Fourier transform infrared (FTIR) spectroscopy revealed that the extraction method (acetic acid and EDTA) did not alter the chemical structures of the ESM and also clarified the composition of the fibrous proteins of the ESM. Scanning electron microscopy (SEM) analyses revealed a three-layer composite structure of the ESM: an inner layer as continuous, dense and non-fibrous (limiting membrane), a middle layer with a network of fibres (inner shell membrane) and the outer layer (outer shell membrane) of larger fibres. Material properties including optical transparency, porosity, fluid absorption/uptake, thermal stability, mechanical profiling of the ESM samples were performed and demonstrated suitable profiles for translational applications. Biological in vitro studies using SV40 immortalised corneal epithelial cells (ihCEC) and corneal mesenchymal stromal cells (C-MSC) demonstrated excellent biocompatibility. Taken together, these results document the development of a novel sustainable biomaterial that may be used for ophthalmic wounds and/or other biomedical therapies.

Quest for Conception: Exploring Treatment Patterns Associated with Infertility in Ghana.

Due to the pronatalist orientation of the Ghanaian society and the social consequences of childlessness, infertile persons adopt several health seeking strategies in their bid to have their own children. This study therefore explored the health seeking behaviour of infertile Ghanaians and the factors that influence this behavior. The study adopted a qualitative research approach. Forty-five semi-structured in-depth interviews were used to collect data. The findings suggest that treatment seeking behaviour of infertile Ghanaians was motivated largely by perceived cause and belief in the efficacy of a treatment form. Two main treatment seeking patterns emerged from the data, hierarchical and concurrent treatment seeking behaviours. Although participants combined spiritual healing with either herbal or orthodox medicine, a combination of orthodox and herbal seemed inappropriate to them. The findings of this study should have implications for healthcare workers in general as the quest for biological parenthood and the treatment seeking behaviours employed by the infertile could be detrimental to the health of these individuals. For instance, the use of unregulated herbalists and itinerant herbal medicine sellers, as well as the over reliance on spiritual healing could have dire implications for health.

Quantification of brain voriconazole levels in healthy adults using fluorine magnetic resonance spectroscopy.

Voriconazole is more effective for aspergillosis infections with central nervous system involvement than other antifungal agents. The clinical efficacy of voriconazole for central nervous system infections has been attributed to its ability to cross the blood-brain barrier. However, pharmacokinetic studies are limited to plasma and cerebrospinal fluid, so it remains unclear how much of the drug enters the brain. Fluorinated compounds such as voriconazole can be quantified in the brain using fluorine-19 magnetic resonance spectroscopy (MRS). Twelve healthy adult males participated in a pharmacokinetic analysis of voriconazole levels in the brain and plasma. Open-label voriconazole was dosed per clinical protocol with a loading dose of 400 mg every 12 h on day 1, followed by 200 mg every 12 h administered orally over a 3-day period. MRS was performed before and after dosing on the third day. Voriconazole levels in the brain exceeded the MIC for Aspergillus. The brain/plasma ratios were 3.0 at steady state on day 3 (predose) and 1.9 postdose. We found that voriconazole is able to penetrate the brain tissue, which can be quantified using a noninvasive MRS technique. (This study has been registered at ClinicalTrials.gov under registration no. NCT00300677.).

Postexercise phosphocreatine recovery, an index of mitochondrial oxidative phosphorylation, is reduced in diabetic patients with lower extremity complications.

OBJECTIVE: To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. METHODS: We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed. RESULTS: The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time. CONCLUSIONS: Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.

Reduced T2* values in soleus muscle of patients with type 2 diabetes mellitus.

Tissue water transverse relaxation times (T2) are highly sensitive to fluid and lipid accumulations in skeletal muscles whereas the related T2* is sensitive to changes in tissue oxygenation in addition to factors affecting T2. Diabetes mellitus (DM) affects muscles of lower extremities progressively by impairing blood flow at the macrovascular and microvascular levels. This study is to investigate whether T2 and T2* are sensitive enough to detect abnormalities in skeletal muscles of diabetic patients in the resting state. T2 and T2* values in calf muscle of 18 patients with type 2 DM (T2DM), 22 young healthy controls (YHC), and 7 age-matched older healthy controls (OHC) were measured at 3T using multi-TE spin echo and gradient echo sequences. Regional lipid levels of the soleus muscle were also measured using the Dixon method in a subset of the subjects. Correlations between T2, T2*, lipid levels, glycated hemoglobin (HbA1c) and presence of diabetes were evaluated. We found that T2 values were significantly higher in calf muscles of T2DM subjects, as were T2* values in anterior tibialis, and gastrocnemius muscles of T2DM participants. However, soleus T2* values of the T2DM subjects were significantly lower than those of the older, age-matched HC cohort (22.9±0.5 vs 26.7±0.4 ms, p<0.01). The soleus T2* values in the T2DM cohort were inversely correlated with the presence of diabetes (t = -3.46, p<0.001) and with an increase in HbA1c, but not with body mass index or regional lipid levels. Although multiple factors may contribute to changes in T2* values, the lowered T2* value observed in the T2DM soleus muscle is most consistent with a combination of high oxygen consumption and poor regional perfusion. This finding is consistent with results of previous perfusion studies and suggests that the soleus in individuals with T2DM is likely under tissue oxygenation stress.

MRI assessment of drug-induced fluid accumulation in humans: validation of the technology.

PURPOSE: The purpose of this study was to evaluate the feasibility of using proton and sodium magnetic resonance imaging (MRI) to detect fluid accumulation produced by fludrocortisone and nifedipine - two drugs known to cause salt/water retention by different mechanisms. MATERIALS AND METHODS: Twelve young healthy male subjects were randomly assigned to one of two groups and treated with either fludrocortisone or nifedipine for 14 or 25 days, respectively. The change in sodium MRI, as well as in proton T(2) value and T(1)-weighted signal intensity in the calf following postural change [referred to here as 'postural delta signal'(PDS)], was evaluated before, during and after drug administration. The changes in MRI PDS were compared to conventional physiological parameters, including body weight, calf volume and pitting edema. RESULTS: When compared to the baseline pretreatment values, the subjects treated with fludrocortisone showed a 5.5% increase in sodium MRI PDS (P=.01), a 2-ms increase in proton T(2) PDS of the gastrocnemius muscle (P=.06) and a body weight gain of 2.3% (P=.001) within 1 week. In the nifedipine-treated subjects, the sodium MRI PDS increased by 6% versus baseline (P=.03), while the proton T(2) PDS of the gastrocnemius muscle increased by 3.7 ms (P=.01), associated with a 0.5% weight gain (P=.55), within 3 weeks. No significant changes were noted in the T(1)-weighed images following postural change. Measurements of calf circumference, volume and pitting edema did not show consistent changes associated with the drug administration. CONCLUSION: The postural change in sodium MRI and proton T(2) signals provides a sensitive method for detecting the fluid accumulation produced by fludrocortisone and nifedipine. The MRI results are consistent with treatment-induced increases in extracellular fluid volume and correlate well with the observed weight gain. These findings support the potential utility of MRI for the evaluation of medication-induced fluid retention.

Whole-system nutrient enrichment increases secondary production in a detritus-based ecosystem.

Although the effects of nutrient enrichment on consumer-resource dynamics are relatively well studied in ecosystems based on living plants, little is known about the manner in which enrichment influences the dynamics and productivity of consumers and resources in detritus-based ecosystems. Because nutrients can stimulate loss of carbon at the base of detrital food webs, effects on higher consumers may be fundamentally different than what is expected for living-plant-based food webs in which nutrients typically increase basal carbon. We experimentally enriched a detritus-based headwater stream for two years to examine the effects of nutrient-induced changes at the base of the food web on higher metazoan (predominantly invertebrate) consumers. Our paired-catchment design was aimed at quantifying organic matter and invertebrate dynamics in the enriched stream and an adjacent reference stream for two years prior to enrichment and two years during enrichment. Enrichment had a strong negative effect on standing crop of leaf litter, but no apparent effect on that of fine benthic organic matter. Despite large nutrient-induced reductions in the quantity of leaf litter, invertebrate secondary production during the enrichment was the highest ever reported for headwater streams at this Long Term Ecological Research site and was 1.2-3.3 times higher than predicted based on 15 years of data from these streams. Abundance, biomass, and secondary production of invertebrate consumers increased significantly in response to enrichment, and the response was greater among taxa with larval life spans < or = 1 yr than among those with larval life spans >1 yr. Production of invertebrate predators closely tracked the increased production of their prey. The response of invertebrates was largely habitat-specific with little effect of enrichment on food webs inhabiting bedrock outcrops. Our results demonstrate that positive nutrient-induced changes to food quality likely override negative changes to food quantity for consumers during the initial years of enrichment of detritus-based stream ecosystems. Longer-term enrichment may impact consumers through eventual reductions in the quantity of detritus.

Proton and sodium MRI assessment of fluid level in calf tissue.

PURPOSE: To investigate the feasibility of using (1)H and (23)Na MRI to detect fluid levels in the lower leg muscle. MATERIALS AND METHODS: Proton and sodium MRI was applied to detect body fluid levels in the lower leg muscles of 18 healthy young male subjects at 3T and 4T. The paradigms under investigation were a postural change from sitting upright to lying supine, and saline infusion. RESULTS: We found that the average proton MR signal in gastrocnemius and soleus muscles were reduced following the postural change by 3.5% +/- 1.4% (P < 0.05) and rose following saline infusion by 3.7% +/- 0.9% (P < 0.01). More dramatically, the sodium MR signal decreased by 7.1% +/- 1.2% (P < 0.01) following the postural change and increased following saline infusion by 12% +/- 3.8% (P < 0.05). The ratio of intra- to extracellular fluid levels was 1.6 +/- 0.5 for the subjects based on the acquired proton and sodium data. CONCLUSION: Our results indicate that proton and sodium MRI can be used to assess fluid levels in the lower extremities, and this technique may be applied to evaluate fluid retention.

[Systematic screening tests for Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in urogenital specimens of infertile couples]. / Existe-t-il un bénéfice au dépistage systématique de Chlamydia trachomatis, Mycoplasma hominis et Ureaplasma urealyticum dans les prélèvements génito-urinaires réalisés au cours d'un bilan d'infertilité?

We conducted a prospective study on 100 couples consulting for infertility at the teaching Hospital of Tours, with the scope to determine if there is a benefit for systematic screening of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum among genito-urinary specimen when exploring couples infertility. C. trachomatis was detected by PCR on sperm, endocervix and urine specimen. M. hominis and U. urealyticum were detected by culture on A7 agar medium and with minigaleries on sperm and endocervix specimen. Standard cultures were also performed on sperm, endocervix, vaginal and urine specimen. Only one specimen (sperm) was positive for C. trachomatis. Three percent of the specimen were positive for U. urealyticum (from which 2,5% of the sperm specimen). No specimen was positive for M. hominis. Our results show that screening of C. trachomatis, M. hominis and U. urealyticum is not systematically required for among check up of infertile couples, given the prevalence of chlamydiosis among the population studied. However, it would be interesting to perform it on a targeted population, according to anamnestic or clinical criteria. In addition, an important modification of vaginal flora was observed in 12% of cases, and 2 vaginosis were diagnosed; the putative consequences of this disequilibrium has to be further investigated.

Reduced anterior cingulate glutamate in pediatric major depression: a magnetic resonance spectroscopy study.

BACKGROUND: Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. METHODS: Fitting to individually quantify anterior cingulate glutamate and glutamine was performed in these subjects with a new basis set created from data acquired on a 1.5 Tesla General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen, Germany). RESULTS: Reduced anterior cingulate glutamate was observed in MDD patients versus control subjects (8.79 +/- 1.68 vs. 11.46 +/- 1.55, respectively, p = .0002; 23% decrease). Anterior cingulate glutamine did not differ significantly between patients with MDD and control subjects. CONCLUSIONS: These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.

A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: A 19-F MRS study.

Racemic fluoxetine consists of R- and S-fluoxetine, which are metabolized to R- and S-norfluoxetine, respectively. This study was designed to compare brain levels achieved with R-fluoxetine to those achieved with racemic fluoxetine in healthy subjects using fluorine-19 (19-F) magnetic resonance spectroscopy (MRS). In all, 13 healthy volunteers received study drug for 5 weeks using a dosing schedule designed to achieve steady state for 20 mg/day racemic fluoxetine, 80 mg/day R-fluoxetine, or 120 mg/day R-fluoxetine. The resulting brain drug levels were measured using 19-F MRS. At 5 weeks, the racemate, 80 and 120 mg/day R-fluoxetine groups had mean brain levels of 25.5, 34.9, and 41.4 microM, respectively. In the serum, R-norfluoxetine, which is thought to be an inactive metabolite, accounted for 17, 71, and 63% of the fluoxetine/norfluoxetine concentration, respectively. When the relative proportion of active to total species in serum are taken into account, the data suggest that doses of R-fluoxetine greater than 120 mg/day would be needed to achieve brain levels of active drug comparable to 20 mg/day of racemate. The 120 mg/day R-fluoxetine group experienced a mean increase in QTc interval of 44 ms, with one individual having an increase of 89 ms, which suggests that higher doses may not be tolerable. While these data support the use of MRS to aid in defining the therapeutic dose range for drug development, they also highlight the need for additional studies with concurrent animal models to establish the validity of using serum drug/metabolite ratios to interpret MRS determined brain drug levels.

S-adenosyl-L-methionine: effects on brain bioenergetic status and transverse relaxation time in healthy subjects.

BACKGROUND: S-adenosyl-L-methionine is an effective treatment for clinical depression, although the mechanism underlying this effect is unclear. Presently, in vivo phosphorus magnetic resonance spectroscopy (31P MRS) and brain transverse relaxometry were employed to test if S-adenosyl-L-methionine supplementation alters brain bioenergetics and/or transverse relaxation time (T2RT) in a nondepressed cohort. If these magnetic resonance techniques are sensitive to S-adenosyl-L-methionine induced alterations in neurochemical processes, these methods may be used in cases of clinical depression to elucidate the mechanism underlying the antidepressant effect of S-adenosyl-L-methionine. METHODS: Twelve subjects self-administered 1600 mg of oral S-adenosyl-L-methionine daily. Phosphorus spectra and transverse relaxation time were acquired at baseline and after treatment using a 1.5 Tesla scanner. RESULTS: Phosphocreatine levels were significantly higher after treatment, whereas beta nucleoside triphosphate levels, predominantly adenosine triphosphate in brain, were significantly lower after treatment. A surprising gender difference in T2RT emerged after supplementation, with women exhibiting significantly lower T2RT than men. CONCLUSIONS: Alterations in phosphocreatine and beta nucleoside triphosphate are consistent with the report that S-adenosyl-L-methionine is involved in the production of creatine, which in turn is phosphorylated to phosphocreatine using adenosine triphosphate. These findings suggest that S-adenosyl-L-methionine alters parameters associated with cerebral bioenergetic status and that some effects of S-adenosyl-L-methionine (T2RT) occur in a gender-specific manner.

Phosphorous31 magnetic resonance spectroscopy after total sleep deprivation in healthy adult men.

STUDY OBJECTIVES: To investigate chemical changes in the brains of healthy adults after sleep deprivation and recovery sleep, using phosphorous magnetic resonance spectroscopy. DESIGN: Three consecutive nights (baseline, sleep deprivation, recovery) were spent in the laboratory. Objective sleep measures were assessed on the baseline and recovery nights using polysomnography. Phosphorous magnetic resonance spectroscopy scans took place beginning at 7 am to 8 am on the morning after each of the 3 nights. SETTING: Sleep laboratory in a private psychiatric teaching hospital. PARTICIPANTS: Eleven healthy young men. INTERVENTIONS: Following a baseline night of sleep, subjects underwent a night of total sleep deprivation, which involved supervision to ensure the absence of sleep but was not polysomnographically monitored. MEASUREMENTS AND RESULTS: No significant changes in any measure of brain chemistry were observed the morning after a night of total sleep deprivation. However, after the recovery night, significant increases in total and beta-nucleoside triphosphate and decreases in phospholipid catabolism, measured by an increase in the concentration of glycerylphosphorylcholine, were observed. Chemical changes paralleled some changes in objective sleep measures. CONCLUSIONS: Significant chemical changes in the brain were observed following recovery sleep after 1 night of total sleep deprivation. The specific process underlying these changes is unclear due to the large brain region sampled in this exploratory study, but changes may reflect sleep inertia or some aspect of the homeostatic sleep mechanism that underlies the depletion and restoration of sleep. Phosphorous magnetic resonance spectroscopy is a technique that may be of value in further exploration of such sleep-wake functions.

Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic resonance spectroscopic imaging study.

The selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome (DS) is an important potential complication of treatment for major depression. We hypothesized that SSRI treatment discontinuation, resulting in change in clinical state, would be associated with reduced rostral anterior cingulate choline (Cho) metabolite ratios. Individuals with a DSM-III-R diagnosis of unipolar major depression who had been stabilized on paroxetine (n = 13) or fluoxetine (n = 13) were study subjects. They were monitored for change in clinical state (mood ratings, discontinuation symptoms) and underwent proton magnetic resonance spectroscopic imaging of the rostral anterior cingulate 3 days after medication substitution with active SSRI and placebo.Placebo-day Cho/Cre (choline/total creatine) metabolite ratios were decreased in four paroxetine and two fluoxetine subjects meeting DS criteria, as compared with asymptomatic subjects (Mann-Whitney z = -2.31, p =.021). Discontinuation syndrome is associated with a rostral anterior cingulate Cho/Cre metabolite ratio decrease that may reflect dynamics of rostral anterior cingulate function.