Botanicals in Postmenopausal Osteoporosis

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.     

A New Care Model Reduces Polypharmacy and Potentially Inappropriate Medications in Long-Term Care

ObjectivesAssess the impact of a new pharmaceutical care model on (1) polypharmacy and (2) potentially inappropriate medication (PIM) use in long-term care facilities (LTCFs).DesignPragmatic quasi-experimental study with a control group. This multifaceted model enables pharmacists and nurses to increase their professional autonomy by enforcing laws designed to expand their scope of practice. It also involves a strategic reorganization of care, interdisciplinary training, and systematic medication reviews.Setting and ParticipantsTwo LTCFs exposed to the model (409 residents) were compared to 2 control LTCFs (282 residents) in Quebec, Canada. All individuals were aged 65 years or older and residing in included LTCFs.MeasuresPolypharmacy (≥10 medications) and PIM (2015 Beers criteria) were analyzed throughout 12 months between March 2017 and June 2018. Groups were compared before and after implementation using repeated measures mixed Poisson or logistic regression models, adjusting for potential confounding variables.ResultsOver 12 months, for regular medications, polypharmacy decreased from 42% to 20% (exposed group) and from 50% to 41% (control group) [difference in differences (DID): 13%, P < .001]. Mean number of PIMs also decreased from 0.79 to 0.56 (exposed group) and from 1.08 to 0.90 (control group) (DID: 0.05, P = .002).Conclusions and ImplicationsCompared with usual care, this multifaceted model reduced the probability of receiving ≥10 medications and the mean number of PIMs. Greater professional autonomy, reorganization of care, training, and medication review can optimize pharmaceutical care. As the role of pharmacists is expanding in many countries, this model shows what could be achieved with increased professional autonomy of pharmacists and nurses in LTCFs.     

Enhancing the multi-dimensional assessment of quality of life: introducing the WHOQOL-Combi

Quality of Life Research - We revisited the global concept of subjective quality of life (QoL) as assessed by the WHOQOL-BREF to investigate whether it could be elaborated into a conceptually more...     

Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated for human papillomavirus (HPV)16, HPV18, and bovine papillomavirus 1 (BPV1). SEAP pseudoviruses were produced by transient transfection of codon-modified papillomavirus structural genes into an SV40 T antigen expressing line derived from 293 cells, yielding sufficient pseudovirus from one flask for thousands of titrations. In a 96-well plate format, in this initial characterization, the assay was reproducible and appears to be as sensitive as, but more specific than, a standard papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The neutralization assay detected type-specific HPV16 or HPV18 neutralizing antibodies (titers of 160-10240) in sera of the majority of a group of women infected with the corresponding HPV type, but not in virgin women. Sera from HPV16 VLP vaccinees had high anti-HPV16 neutralizing titers (mean: 45000; range: 5120-163840), but no anti-HPV18 neutralizing activity. The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies.     

Comparison of adipose stem cells sources from various locations of rat body for their application for seeding on polymer scaffolds

Adipose tissue yields adult adipose stem cells (ASCs) in large quantities via less-invasive methods. These cells are of interest owing to their modulating properties and paracrine activities, which can be harnessed in regenerative medicine. Many studies on the use of rat fat tissue in an autologous animal model have been conducted; however, the different locations to obtain stromal vascular fraction of rat fat depots have not been fully characterized. The purpose of the current study was to identify optimal source of ASC from various locations of rat body. Animal experiments in vitro revealed that fat depots from cervical fat are an optimal ASC source. A high ASC yield facilitates subsequent studies on autologous transplantation in rats. The secondary objective was to compare the efficiency of osteoinductive media composition and evaluate of osteogenic potential of ASCs for seeding on scaffolds for bone repair. Scaffolds were assessed in vitro, using rat adipose stem cells and three-dimensional (3D) scaffolds comprising polycaprolactone (PCL) or polycaprolactone covered with tricalcium phosphate (PCL + 5%TCP). Seeded ASCs adhere to the surface and migrate to the scaffolds. Upon staining and determining alkaline phosphatase levels, PCL + 5%TCP scaffolds performed better than PCL scaffolds. Furthermore, growth factors such as BMP2 and FGF2 significantly increased ASC mineralization and induced osteogenesis (p?<?0.05). Our results may help select and develop pre-clinical animal model for confirming the use of ASC, alone or in association with appropriate biomaterials for bone repair.     

Long-term persistence of specific T- and B-lymphocyte responses to Borrelia burgdorferi following untreated neuroborreliosis

Summary Follow-up studies on 56 patients who suffered from antibiotically untreated, acute, monophasic neuroborreliosis five to 23 years ago revealed significant positive levels of IgG antibodies toBorrelia burgdorferi (Bb) in the serum and cerebrospinal fluid (CSF) of 20 patients (IFT, ELISA, Bb-specific IgG Western blot, Bb-specific IEF-IgG immunoblot). Nine of 10 tested patients had a definitely positive T-cell proliferative response to wholeB. burgdorferi, with a mean (±-SEM) stimulation index of 7.2±1.8. Because the patients studied exhibited no, or only mild to medium sequelae without any evidence of a chronic-progressive disease, we interpret the long-term persistence of specific T- and B-lymphocyte responses toB. burgdorferi as an immunological scar syndrome. Finally, diagnostic criteria of active neuroborreliosis are proposed.

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Langzeit-Persistenz der spezifischen T- und B-Lymphozyten — Antworten auf Borrelia burgdorferi nach unbehandelter Neuroborreliose

Zusammenfassung Verlaufsuntersuchungen von 56 Patienten, die vor fünf bis 23 Jahren an einer antibiotisch nicht behandelten, akuten monophasischen Neuroborreliose erkrankt waren, zeigten signifikant positive IgG-Antikörpertiter fürBorrelia burgdorferi im Serum und Liquor von 20 Patienten (IFT, ELISA,B. burgdorferi-spezifischer IgG-Westernblot,B. burgdorferi-spezifischer IEF-IgG-Immunoblot). Neun von zehn getesteten Patienten wiesen eine signifikant positive T-Zellproliferationsantwort gegenüber dem gesamtenB. burgdorferi-Antigen mit einem mittleren (±SEM) Stimulationsindex von 7.2±1.8 auf. Da die untersuchten Patienten keine oder nur leichte bis mittelgradige Residualsymptome ohne irgendeinen Hinweis auf eine chronisch-progressive Krankheit hatten, interpretierten wir die Langzeit-Persistenz der spezifischen T- und B-Lymphozytenantworten fürB. burgdorferi als ein immunologisches Narbensyndrom. Abschließend werden diagnostische Kriterien der aktiven Neuroborreliose vorgeschlagen.

     

Pharmacokinetics and haemodynamic effects of a single oral dose of the novel ACE inhibitor spirapril in patients with chronic liver disease

Summary The pharmacokinetics and haemodynamic effects of orally administered spirapril, a novel angiotensinconverting enzyme (ACE) inhibitor, have been investigated in patients with liver cirrhosis (n=10), in patients with chronic, non-cirrhotic liver disease (n=8) and in a control group of healthy subjects (n=16).The absorption and elimination of spirapril did not differ between patients with liver disease and control subjects. In contrast, the bioavailability of spiraprilat, the metabolite responsible for the pharmacological action of spirapril, was significantly reduced in patients (AUC 820 g·h·l^–1, 923 g·h·l^–1 and 1300 g·h·l^–1 in patients with cirrhosis, patients with non-cirrhotic liver disease and in healthy subjects, respectively.Compared to healthy subjects, cirrhotic patients had a reduced rate constant of spiraprilat formation (1.10 h^–1 in patients vs. 2.00 h^–1 in control subjects) while the elimination half-life of spiraprilat was not different. The effect of spirapril on diastolic blood pressure was decreased in patients with chronic liver disease as compared to the controls.Thus, the pharmacokinetics of spirapril was unchanged in patients with different types of liver disease, including cirrhosis. However, the bioavailability of spiraprilat and hypotensive effect of spirapril were reduced in patients.     

Selenium in serum as a possible parameter for assessment of breast disease

Summary The level of selenium in blood serum was determined in 33 patients with breast cancer, 13 women with verified mastopathy, and 43 healthy subjects from the Zagreb area. In the second and third quartiles the values of selenium obtained from sick subjects (41–58µg/L) and healthy subjects (73–89µg/L) differed significantly (P < 0.001). In the group of subjects with mastopathy, serum selenium in the same way ranged from 67–76µg/L and did not differ significantly from the group of healthy women, but differed significantly from the patients with breast cancer (P < 0.001).Such a result leads to the conclusion that determination of selenium in the blood could be used as a non-invasive diagnostic parameter in clinical assessment of malignant breast disease.     

DNA measurement,proliferation markers,and other factors in pituitary adenomas

To assess the proliferative activity of pituitary adenomas, 36 surgically removed adenomas were studied by light microscopical parameters; mitotic count; expression of PCNA, Ki-67, cathepsin D, and EGF; and image cytometry. Three adenomas (9%) showed high, 11 (34%) medium, 17 (53%) moderate, and 1 (3%) low structural differentiation. In 10 adenomas (31%), no mitosis was observed. The average was 2.4 mitoses/100 HPF; the highest count was 7.1 mitoses/100 HPF. Eleven adenomas (33.3%) were PCNA-negative; in 20 adenomas (60.6%), between 0.05 and 3.9, and in 2 adenomas (6.0%), between 10.5 and 16.4 PCNA-positive nuclei were observed. Only a recurrent null-cell adenoma (9%) was Ki-67-negative. Three adenomas (9.1%) were EGF-negative, 28 (84.8%) showed up to 10% positive cells, and 2 (6.1 %) showed between 10 and 30% positive cells; 19 adenomas (68%) were cathepsin D-negative, including all endocrine-inactive adenomas. Half the adenomas had an euploid DMA stem line. Endocrine-inactive adenomas displayed a higher rate of euploid DNA stem lines than endocrine-active adenomas. The S-phase fraction varied between 2.97 and 28%, with a mean value of 14.4%. Half the adenomas showed an S-phase fraction of 11.65% or lower.