The absorption and uptake of recombinant human follicle-stimulating hormone through vaginal subcutaneous injections - a pharmacokinetic study

<p>Abstract</p> <p>Background</p> <p>Follicle stimulating hormone (FSH) has been routinely used for ovulation induction. Because of rapid clearance of the hormone, FSH is commonly administered by daily intramuscular or subcutaneous injections in in-vitro fertilization (IVF). To reduce the number of visits to the clinic, an intermittent vaginal injection of rhFSH every 3 days employing the concepts of mesotherapy and uterine first-pass effect was invented and has successfully been applied in women receiving IVF treatment. This study was designed to monitor the pharmacokinetic pattern of rhFSH administered vaginally.</p> <p>Methods</p> <p>Twelve healthy women with regular ovulatory cycles were recruited. All volunteers received gonadotrophin-releasing hormone agonist to suppress pituitary function and were assigned to receive single dose recombinant human FSH (rhFSH, Puregon 300) either using conventional abdominal subcutaneous injection or vaginal subcutaneous injection in a randomized cross-over study. Serum samples were collected at pre- scheduled time intervals after injections of rhFSH to determine immunoreactive FSH levels. Pharmacokinetic parameters characterizing rate [maximal plasma concentrations (Cmax) and time of maximal plasma concentrations (tmax)] and extent [area under the plasma concentration-time curve (AUC) and clearance] of absorption of rhFSH were compared.</p> <p>Results</p> <p>Vaginal injection of rhFSH was well tolerated and no drug-related adverse reaction was noted. Our analysis revealed that tmax was significantly earlier (mean 6.67 versus 13.33 hours) and Cmax was significantly higher (mean 17.77 versus 13.96 IU/L) in vaginal versus abdominal injections. The AUC_0-∞ was 1640 versus 1134 IU·hour/L in vaginal and abdominal injections, respectively. Smaller plasma elimination rate constant (0.011 versus 0.016 hour-1), longer mean residence time (106.58 versus 70.47 hours), and slower total body clearance (292.2 versus 400.1 mL/hour) were also found in vaginal injection.</p> <p>Conclusion</p> <p>The vaginal injection mode elicited a rapid and highly extended absorption of rhFSH injected compared to conventional abdominal injection. These data indicate that the rate and extent of FSH absorption from the injection site can vary depending on the route of the FSH administration.</p

Efficient Downlink Channel Reconstruction for FDD Multi-Antenna Systems

In this paper, we propose an efficient downlink channel reconstruction scheme for a frequency-division-duplex multi-antenna system by utilizing uplink channel state information combined with limited feedback. Based on the spatial reciprocity in a wireless channel, the downlink channel is reconstructed by using frequency-independent parameters. We first estimate the gains, delays, and angles during uplink sounding. The gains are then refined through downlink training and sent back to the base station (BS). With limited overhead, the refinement can substantially improve the accuracy of the downlink channel reconstruction. The BS can then reconstruct the downlink channel with the uplink-estimated delays and angles and the downlink-refined gains. We also introduce and extend the Newtonized orthogonal matching pursuit (NOMP) algorithm to detect the delays and gains in a multi-antenna multi-subcarrier condition. The results of our analysis show that the extended NOMP algorithm achieves high estimation accuracy. Simulations and over-the-air tests are performed to assess the performance of the efficient downlink channel reconstruction scheme. The results show that the reconstructed channel is close to the practical channel and that the accuracy is enhanced when the number of BS antennas increases, thereby highlighting that the promising application of the proposed scheme in large-scale antenna array systems

AN AUTOPSY CASE OF PARATHYROID CARCINOMA

A case of hyperfunctioning parathyroid carcinoma was found in a 78-year-old female who had suffered from hypercalcemia for 5 years. She died of renal failure and pulmonary edema. Autopsy revealed an encapsulated tumor arising from the left upper parathyroid gland. Histologically, fibrous trabeculae, capsular invasion and blood vessel invasion were occasionally present in this tumor, suggesting that this tumor was malignant. However, mitotic figures were rarely observed. We reviewed reported cases of parathyroid carcinoma and discussed about the significance of mitosis for diagnosis

Morphometrical Study on the Sclerotic Inferior Vena Cava in Chronic Lung Disease

The purpose of this study is to determine the relationship between chronic lung disease (CLD) and morphological changes in the inferior vena cava (IVC) from postmortem materials. The IVC and pulmonary truncus were obtained from 70 cases with CLD and/or cor pulmonale and from 23 controls. The tissues were processed for light and electron microscopic studies. The adventitia was by far the thickest component of the IVC wall. The total wall, intimal, and adventitial thicknesses were all significantly greater in the CLD cases than in the controls (p<0.001), but there was no significant difference in the ratio of adventitia thickness to wall thickness. The incidence of intimal thickening was 13.0% and 37.3% in controls and in CLD respectively. Electron microscopic examination of the IVC from the CLD cases revealeda marked increase in the amount of extracellular matrix including collagen, elastic fibers and ground substances in the adventitia as compared with the controls. No foam cells were detected in the thickened intima of the IVC. PA, right ventricular thickness and RV/LV ratio were greater in CLD than in controls. The blood gas levels of the CLD cases indicated obvious hypoxia (PaO2 54.2 mmHg). This study suggests that increased venous pressure and hypoxia might be implicated in the pathogenesis of phlebosclerosis in patients with CLD

Purification and differentiation of human adipose-derived stem cells by membrane filtration and membrane migration methods

Human adipose-derived stem cells (hADSCs) are easily isolated from fat tissue without ethical concerns, but differ in purity, pluripotency, differentiation ability, and stem cell marker expression, depending on the isolation method. We isolated hADSCs from a primary fat tissue solution using: (1) conventional culture, (2) a membrane filtration method, (3) a membrane migration method where the primary cell solution was permeated through membranes, adhered hADSCs were cultured, and hADSCs migrated out from the membranes. Expression of mesenchymal stem cell markers and pluripotency genes, and osteogenic differentiation were compared for hADSCs isolated by different methods using nylon mesh filter membranes with pore sizes ranging from 11 to 80 μm. hADSCs isolated by the membrane migration method had the highest MSC surface marker expression and efficient differentiation into osteoblasts. Osteogenic differentiation ability of hADSCs and MSC surface marker expression were correlated, but osteogenic differentiation ability and pluripotent gene expression were not

Blockchain-Based Medical Record Management with Biofeedback Information

Blockchain is a new emerging technology of distributed databases, which guarantees the integrity, security and incorruptibility of data by means of the cryptography. Such features are suitable for secure and reliable data storage. This chapter investigates the blockchain-based architecture with applications to medical health record or biofeedback information management. This framework employs the smart contract to establish a medical record management system to ensure the privacy of patients. Moreover, the blockchain technique accelerates the medical record or information exchange such that the cost of human resource is significant reduced. All patients can manage their individual medical records and information easily in the different hospitals and clinics. They also have the privilege to deal with and authorize personal medical records in the proposed management framework

A retrospective analysis of 20-year data of the surgical management of ulcerative colitis patients in Taiwan: a study of Taiwan Society of Inflammatory Bowel Disease

Background/AimsWith the recent progress in medical treatment, surgery still plays a necessary and important role in treating ulcerative colitis (UC) patients. In this study, we analyzed the surgical results and outcomes of UC in Taiwan in the recent 20 years, via a multi-center study through the collaboration of Taiwan Society of IBD.MethodsA retrospective analysis of surgery data of UC patients from January 1, 1995, through December 31, 2014, in 6 Taiwan major medical centers was conducted. The patients' demographic data, indications for surgery, and outcome details were recorded and analyzed.ResultsThe data of 87 UC patients who received surgical treatment were recorded. The median post-operative follow-up duration was 51.1 months and ranged from 0.4 to 300 months. The mean age at UC diagnosis was 45.3±16.0 years and that at operation was 48.5±15.2 years. The 3 leading indications for surgical intervention were uncontrolled bleeding (16.1%), perforation (13.8%), and intractability (12.6%). In total, 27.6% of surgeries were performed in an emergency setting. Total or subtotal colectomy with rectal preservation (41.4%) was the most common operation. There were 6 mortalities, all due to sepsis. Emergency operation and low pre-operative albumin level were significantly associated with poor survival (P=0.013 and 0.034, respectively).ConclusionsIn the past 20 years, there was no significant change in the indications for surgery in UC patients. Emergency surgeries and low pre-operative albumin level were associated with poor survival. Therefore, an optimal timing of elective surgery for people with poorly controlled UC is paramount

A molten globule-to-ordered structure transition of Drosophila melanogaster crammer is required for its ability to inhibit cathepsin

Drosophila melanogaster crammer is a novel cathepsin inhibitor that is involved in LTM (long-term memory) formation. The mechanism by which the inhibitory activity is regulated remains unclear. In the present paper we have shown that the oligomeric state of crammer is pH dependent. At neutral pH, crammer is predominantly dimeric in vitro as a result of disulfide bond formation, and is monomeric at acidic pH. Our inhibition assay shows that monomeric crammer, not disulfide-bonded dimer, is a strong competitive inhibitor of cathepsin L. Crammer is a monomeric molten globule in acidic solution, a condition that is similar to the environment in the lysosome where crammer is probably located. Upon binding to cathepsin L, however, crammer undergoes a molten globule-to-ordered structural transition. Using high-resolution NMR spectroscopy, we have shown that a cysteine-to-serine point mutation at position 72 (C72S) renders crammer monomeric at pH 6.0 and that the structure of the C72S variant highly resembles that of wild-type crammer in complex with cathepsin L at pH 4.0. We have determined the first solution structure of propeptide-like protease inhibitor in its active form and examined in detail using a variety of spectroscopic methods the folding properties of crammer in order to delineate its biomolecular recognition of cathepsin

Efficacy of pharmacologic treatment in tinnitus patients without specific or treatable origin: A network meta-analysis of randomised controlled trials

Background- Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear. Methods- The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5th, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742. Findings- Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control. Interpretation- The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin