Boosting the thermal management performance of a PCM-based module using novel metallic pin fin geometries: Numerical study.

Satellite avionics and electronic components are getting compact and have high power density. Thermal management systems are essential for their optimal operational performance and survival. Thermal management systems keep the electronic components within a safe temperature range. Phase change materials (PCMs) have high thermal capacity, so they are promising for thermal control applications. This work adopted a PCM-integrated thermal control device (TCD) to manage the small satellite subsystems under zero gravity conditions thermally. The TCD's outer dimensions were selected upon a typical small satellite subsystem. The PCM adopted was the organic PCM of RT 35. Pin fins with different geometries were adopted to boost the lower thermal conductivity of the PCM. Six-pin fins geometries were used. First, the conventional geometries were square, circular, and triangular. Second, the novel geometries were cross-shaped, I-shaped, and V-shaped fins. The fins were designed at two-volume fractions of 20% and 50%. The electronic subsystem was assumed to be "ON" for 10 min releasing 20 W of heat, and "OFF" for 80 min. The findings show a remarkable decrease in the TCD's base plate temperature by 5.7 ℃ as the fins' number changed from 15 to 80 for square fins. The results also show that the novel cross-shaped, I-shaped, and V-shaped pin fins could significantly enhance thermal performance. The cross-shaped, I-shaped, and V-shaped reported a decrease in the temperature by about 1.6%, 2.6%, and 6.6%, respectively, relative to the circular fin geometry. V-shaped fins could also increase the PCM melt fraction by 32.3%.

The effect of risankizumab on achieving minimal clinically important differences in patient-reported outcomes in patients with psoriatic arthritis: results from KEEPsAKE 1 and 2.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that reduces the quality of life. This study assessed the effects of risankizumab (RZB) on the achievement of minimal clinically important differences (MCID) in patient-reported outcomes (PROs). METHODS: KEEPsAKE-1 and -2 are randomized, placebo-controlled Phase 3 clinical studies assessing RZB (150 mg) vs. placebo (PBO) in adult patients with PsA with inadequate response or intolerance to disease-modifying antirheumatic drugs and/or biologics. Patients were randomized 1:1 to receive RZB or PBO for 24 weeks; starting at Week 24, all patients received RZB 150 mg through Week 52. PROs assessed were Patient's Global Assessment of Disease Activity (PtGA), Patient's Assessment of Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form 36 Physical and Mental Component Summary scores (PCS and MCS, respectively), 5-Level EQ-5D (EQ-5D-5L), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and Work Productivity and Activity Impairment (WPAI). The proportion of patients achieving MCID at Weeks 24 and 52 are reported. Odds ratios of achieving MCID with RZB treatment at Week 24, relative to PBO, were estimated by logistic regression controlling for baseline and stratification factors. RESULTS: In KEEPsAKE-1, RZB- vs. PBO-treated patients were more likely to report MCID in all PROs at Week 24; similar results were obtained in KEEPsAKE-2, except for SF-36 MCS and WPAI presenteeism domain. In KEEPsAKE-1 and KEEPsAKE-2, 65% and 62% of RZB-treated patients, respectively, reported MCID in PtGA at Week 24, which increased to 74% and 68%, respectively, at Week 52. Approximately 48% of all PBO-treated patients reported MCID in PtGA at Week 24 and, after initiating RZB, >65% reported MCID at Week 52. Results were similar in the remaining PROs. CONCLUSIONS: These data demonstrate that patients with PsA receiving RZB treatment are more likely to report clinically important improvements in PROs compared with patients receiving PBO.

Long-term, durable, absolute Psoriasis Area and Severity Index and health-related quality of life improvements with risankizumab treatment: a post hoc integrated analysis of patients with moderate-to-severe plaque psoriasis.

BACKGROUND: Risankizumab has demonstrated durable, high rates of efficacy in patients with moderate-to-severe plaque psoriasis as assessed by the achievement of relative Psoriasis Area and Severity Index (PASI) improvement and Dermatology Life Quality Index (DLQI) 0/1. OBJECTIVES: The aim of this post hoc analysis is to assess the achievement of absolute PASI thresholds and related improvements in health-related quality of life (HRQoL) in patients with moderate-to-severe plaque psoriasis treated with (i) risankizumab compared with ustekinumab, and (ii) long-term (>52 weeks to 172 weeks) risankizumab. METHODS: Data from patients randomised to 150 mg risankizumab or 45 or 90 mg ustekinumab in replicate randomised controlled trials UltIMMa-1 and UltIMMa-2 were analysed for the achievement of absolute PASI thresholds PASI ≤ 3, PASI ≤ 1, and PASI = 0, time to achieve these thresholds, and combined PASI and DLQI endpoints. Data from pat ients initially randomised to risankizumab who continued on risankizumab in the open-label extension study LIMMitless were analysed for the achievement of absolute PASI levels, mean DLQI scores, and DLQI 0/1. RESULTS: Significantly greater proportions of patients treated with risankizumab compared with ustekinumab achieved PASI ≤ 3, PASI ≤ 1, and PASI = 0, as well as combined endpoints for absolute PASI and DLQI [(PASI ≤ 3 and DLQI ≤ 5) or (PASI ≤ 1 and DLQI 0/1)]. The median time to first achieve PASI ≤ 3, PASI ≤ 1, and PASI = 0 was significantly lower for risankizumab-treated patients compared with ustekinumab-treated patients. Among patients treated with long-term risankizumab, more than 90% achieved PASI ≤ 3 though week 172 and more than 80% achieved DLQI 0/1. Low absolute PASI scores corresponded with low mean absolute DLQI scores through week 172 of continuous risankizumab treatment. CONCLUSIONS: Risankizumab treatment demonstrated high rates of rapid and durable efficacy as measured by absolute PASI thresholds and improvements in patient HRQoL.

Long-term efficacy and safety of risankizumab for the treatment of moderate-to-severe plaque psoriasis: interim analysis of the LIMMitless open-label extension trial beyond 3 years of follow-up.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease requiring prolonged treatment. New biologic therapies require long-term evaluation to assess the durability of their efficacy and safety profiles over time. OBJECTIVES: To evaluate the long-term efficacy and safety of risankizumab (RZB) for the treatment of psoriasis. METHODS: LIMMitless is an ongoing, phase III, open-label extension study evaluating the long-term efficacy and safety of RZB in adults with moderate-to-severe plaque psoriasis following multiple phase II/III studies. This analysis assessed efficacy through 172 weeks of continuous RZB treatment by examining the proportion of patients achieving ≥ 90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90 and PASI 100), static Physician's Global Assessment of clear or almost clear (sPGA 0/1) and Dermatology Life Quality Index of no effect on quality of life (DLQI 0/1). Safety was assessed by recording adverse events (AEs) through the data cutoff date. The study is registered at ClinicalTrials.gov (identifier: NCT03047395). RESULTS: Of 955 patients randomized to RZB 150 mg in the base studies, 897 patients continued into LIMMitless; 799 patients were still receiving treatment in LIMMitless at the time of data cutoff for this analysis. After 172 weeks of continuous RZB treatment, 85·5% of patients achieved PASI 90, 54·4% achieved PASI 100, 85·2% achieved sPGA 0/1, and 78·4% achieved DLQI 0/1 using modified nonresponder imputation. Rates of AEs leading to discontinuation and AEs of safety interest were low with long-term treatment and comparable with those identified in the base studies. CONCLUSIONS: Overall, long-term continuous RZB was well tolerated and showed high and durable efficacy over 172 weeks.

Patient-reported outcomes with risankizumab versus fumaric acid esters in systemic therapy-naïve patients with moderate to severe plaque psoriasis: a phase 3 clinical trial.

BACKGROUND: In a phase 3 clinical study, patients from Germany with moderate to severe psoriasis who were naïve to systemic treatment and received risankizumab had greater and more rapid disease improvements compared with those who received fumaric acid esters (FAEs). OBJECTIVE: To evaluate patient-reported outcomes (PROs) in patients treated with risankizumab compared with FAEs. METHODS: Adult patients were randomized 1:1 to receive either risankizumab 150 mg subcutaneous injections at weeks 0, 4 and 16 or FAEs (Fumaderm® ) provided according to the prescribing label. PRO secondary endpoints assessed were Psoriasis Symptom Scale (PSS), Dermatology Life Quality Index (DLQI), 36-Item Short Form Health Survey, version 2 (SF-36v2), Patient Benefit Index (PBI), Hospital Anxiety and Depression Scale (HADS), Patient Global Assessment (PtGA) and European Quality of Life 5 Dimensions 5 Level (EQ-5D-5L). PROs were assessed at weeks 0, 16 and 24. RESULTS: Sixty patients each were randomized to receive risankizumab or FAEs. A significant PSS improvement was observed with risankizumab vs. FAEs at weeks 16 and 24 for total and psoriasis-associated redness, itching and burning scores (P < 0.001). DLQI scores were significantly lower (reflecting better health-related quality of life) with risankizumab vs. FAEs, with least squares (LS) mean differences of -7.4 and -7.6 at weeks 16 and 24, respectively (both P < 0.001). Patients randomized to risankizumab also had larger improvements in SF-36 Physical and Mental Component Summary scores, HADS anxiety and depression scores, PtGA, and EQ-5D-5L index and visual analogue scale scores (all P ≤ 0.002) at weeks 16 and 24 compared with FAEs. PBI was significantly higher, indicating greater benefit, with risankizumab vs. FAEs, with an LS mean difference of 1.1 and 1.3 at weeks 16 and 24, respectively (both P < 0.001). CONCLUSIONS: Risankizumab provides significant benefits over FAEs in improving PROs across several dimensions in patients with moderate to severe psoriasis.

Effects of probiotic and Bidens pilosa on the performance and gut health of chicken during induced Eimeria tenella infection.

AIM: In this study, we have examined the individual and combined protective mechanism of probiotic and Bidens pilosa on the performance and gut health of chickens during Eimeria tenella infection over a 29-day experimental trial. METHODS AND RESULTS: A total of one hundred and fifty 1-day-old chickens were equally distributed into five treatment groups with three biological replicates: two groups were allocated as control groups (control group untreated unchallenged, CG and control positive untreated challenged, CPG) and three groups were fed diets with probiotic (PG), B. pilosa (BPG) and probiotic + B. pilosa (PG + BPG) and challenged with E. tenella. Birds of all groups were assessed for pre and post-infection body weights, oocysts shedding, caecal lesion scores and mRNA expression levels of apoptosis related proteins (Bcl-2, Bax and caspase-3), antioxidant enzymes (CAT and SOD 1), pro-inflammatory cytokines (IL-6 and IL-8) and tight junction proteins (CLDN 1 and ZO 1). Our results revealed that during infection (day 21-29), E. tenella challenged chickens significantly decreased the body weight compared with uninfected control chickens; however, there was no significant effect on body weight of chickens fed with probiotic, B. pilosa and probiotic + B. pilosa was observed. Eimeria tenella challenged untreated birds increased (P < 0·05) oocysts shedding, destructive ratio of caeca and mortality as compared to treated challenged birds. CPG group up-regulated the mRNA expression levels of anti-apoptosis protein Bcl-2 while down-regulated the pro-apoptosis protein Bax relative to PG, BPG and PG + BPG groups. Moreover chickens fed probiotic, B. pilosa and probiotic + B. pilosa diets enhanced the activities of antioxidant enzymes, pro-inflammatory cytokines and tight junction proteins with the comparison of control positive untreated challenged chickens. CONCLUSION: These findings elaborated that feed supplementation of probiotic and B. pilosa (individually or in combination) appeared to be effective in inhibiting the occurrence of disease and decreasing the severity of Eimeria infection in chickens. SIGNIFICANCE AND IMPACT OF THE STUDY: This study explained the underlying anti-coccidial mechanism in which probiotic and B. pilosa (individually and/or in combination) improve the performance of chicken and protect against gut inflammatory responses caused by E. tenella.

Pharmacokinetics and tissue residue of enrofloxacin in healthy, Eimeria-infected broiler chickens and those pre-treated with amprolium and toltrazuril.

The pharmacokinetics of enrofloxacin was compared in healthy chickens, Eimeria infected chickens and in Eimeria infected chickens pre-treated with amprolium or toltrazuril following a single IV and oral administration at dose 10 mg/kg. The blood samples were taken after administration at different time intervals (5 min to 24 hours) to determine the pharmacokinetic parameters of enrofloxacin. The different concentrations of enrofloxacin were determined by using HPLC assay method. Serum concentrations versus time were analysed by a non-compartmental method. The results explored a significant decrease in serum concentrations of enrofloxacin at different time intervals and a significant change in pharmacokinetic profiles in Eimeria infected chickens compared with those values in healthy chickens whereas, amprolium improves these values. Toltrazuril leads to a significant decrease in enrofloxacin concentrations compared with infected non-treated chickens. Multiple-dose study revealed a longer withdrawal period of enrofloxacin in infected non-treated and infected chickens pre-treated with amprolium compared with the healthy group.

Healthcare utilization and cost burden among women with endometriosis by opioid prescription status in the first year after diagnosis: a retrospective claims database analysis.

Aims: Opioids do not represent standard therapy for endometriosis; however, women with endometriosis are frequently prescribed an opioid to manage related abdominal or pelvic pain. The aim of this study was to evaluate the impact of opioid use on endometriosis-related economic and healthcare burden in the United States.Materials and methods: We performed a retrospective, propensity-matched cohort analysis of the Truven MarketScan Commercial database from 1 January 2011 to 31 December 2016. Eligible women had at least 1 inpatient or 2 outpatient codes for endometriosis and 12 months of continuous enrollment before and after the index date (i.e. first recorded endometriosis diagnosis). The primary analysis examined healthcare costs and utilization for 12 months after the index date in women who filled at least 1 opioid prescription versus those who did not. The secondary analysis examined healthcare costs and utilization by the pattern of opioid use.Results: The primary analysis matched 43,516 women across 2 groups and the secondary analysis matched 13,230 women across 5 groups. In the primary analysis, total 12-month healthcare costs were significantly higher in the opioid group compared to the non-opioid group ($29,236.00 vs. $18,466.00, respectively; p < .001); the same pattern was observed for all healthcare utilization parameters. In the secondary analysis, higher morphine equivalent daily dose and proportion of days covered were associated with the highest healthcare costs and utilization compared to the non-opioid group.Limitations: Retrospective design and inability to confirm whether filled opioid prescriptions were actually taken.Conclusions: Filling an opioid prescription within 1 year after an endometriosis diagnosis was associated with significant excess healthcare burden. Patients prescribed an opioid may experience inadequate symptom management and benefit from the use of disease-specific, non-opioid therapies.

Ex vivo ovine model for suspension microlaryngoscopy training.

OBJECTIVE: To develop an ovine model for teaching suspension laryngoscopy and phonosurgery. METHODS: The head and neck from 10 pre-pubescent sheep were harvested following humane euthanasia at the end of an in vivo protocol. No live animals were used in this study. The tissues were saline-perfused and refrigerated for 1-5 days. Suspension laryngoscopy was performed using adolescent Parsons and adult Kantor-Berci laryngoscopes suspended with a Benjamin-Parsons laryngoscope holder. Visualisation was achieved with 0° and 30° telescopes, and a three-chip camera and video system. Shapshay-Ossoff microlaryngeal instruments were used for endolaryngeal dissection. RESULTS: Experienced laryngologists led a second year medical student through several procedures including injection laryngoplasty, hydrodissection and incision, endolaryngeal suturing, and partial cordectomy. Despite expected anatomical differences, the model proved highly realistic for suspension microlaryngoscopy. CONCLUSION: The sheep head and neck model provides an inexpensive, safe model for developing skills in suspension laryngoscopy and basic phonosurgery.

Study of Using Solar Thermal Power for the Margarine Melting Heat Process.

The heating process of melting margarine requires a vast amount of thermal energy due to its high melting point and the size of the reservoir it is contained in. Existing methods to heat margarine have a high hourly cost of production and use fossil fuels which have been shown to have a negative impact on the environment. Thus, we perform an analytical feasibility study of using solar thermal power as an alternative energy source for the margarine melting process. In this study, the efficiency and cost effectiveness of a parabolic trough collector (PTC) solar field are compared with that of a steam boiler. Different working fluids (water vapor and Therminol-VP1 heat transfer oil (HTO)) through the solar field are also investigated. The results reveal the total hourly cost ($/h) by the conventional configuration is much greater than the solar applications regardless of the type of working fluid. Moreover, the conventional configuration causes a negative impact to the environment by increasing the amount of CO2, CO, and NO2 by 117.4 kg/day, 184 kg/day, and 74.7 kg/day, respectively. Optimized period of melt and tank volume parameters at temperature differences not exceeding 25 °C are found to be 8-10 h and 100 m3, respectively. The solar PTC operated with water and steam as the working fluid is recommended as a vital alternative for the margarine melting heating process.

Stump appendicitis: an uncompleted surgery, a rare but important entity with potential problems.

Appendicectomy for appendicitis is one of the commonest surgical procedures performed worldwide. The residual appendiceal stump left after an initial appendectomy risks the development of stump appendicitis. Stump appendicitis is a real recognized entity but not often considered when evaluating patients with right lower quadrant abdominal pain, especially those with past history of appendectomy. It remains a clinical challenge with the result that its diagnosis and effective treatment are often delayed with possible attendant morbidity or mortality. Stump appendicitis results from obstruction of the lumen of the remaining appendix stump, usually by a faecolith. This increases intraluminal pressure, impairing venous drainage and allowing subsequent bacterial infection. We present the case of a twenty-five (25)-year-old female who underwent laparoscopic appendicectomy and presented four and half (4(1/2)) months later with fever, right lower quadrant abdominal pain, and tenderness associated with repeated vomiting. Exploratory laparotomy was carried out after clinical and imaging studies which revealed big inflammatory mass with abscess at the right iliac fossa and recurrent appendicitis of the appendiceal stump. Surgical treatment is easy but recognition of this important entity but potentially dangerous condition should always be borne in mind in order to avoid delay in its diagnosis and treatment.

Hypoglycemic and antioxidative effects of fenugreek and termis seeds powder in streptozotocin-diabetic rats.

BACKGROUND AND OBJECTIVES: Diabetes mellitus is a heterogeneous disease characterized by altered cellular metabolism. So, many traditional herbs are being used by diabetic patients to control this disease. In the present study, an attempt has been made to investigate the anti-diabetic and antioxidative effects of water suspension of Fenugreek (F), and Termis (T) seeds powder and their mixture (M) who were studied in Streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: Experimental diabetes was induced by injection a single dose of STZ (50 mg/kg, i.p.). Adult male albino rats were divided into five groups; normal control, diabetic control, diabetic-F supplement (1 g/kg b.wt.), diabetic-T supplement (1 g/kg b.wt.) and diabetic-M supplement 1 g/kg b.wt. of each seed powder concurrently for 30 days. Serum glucose, insulin, lipid profile, activities of serum marker enzymes of liver function as well as liver and muscle glycogen content were measured. The oxidative stress was assessed by blood reduced glutathione (GSH) content and enzyme activities of glutathione-S-transferase (GST) and catalase (CAT) in plasma. RESULTS: The increase in serum glucose, total lipid, triglycerides, total cholesterol, AST, ALT, ALP and decreased insulin, plasma, GSH, GST, CAT, as well as liver and muscle glycogen content were the salient features recorded in diabetic control rats. The F, T and M supplements significantly reverted the levels of the studied metabolites and enzymes activities to near normal control values. Co-administration of F and T seeds powder was considered as an effective agent in modulating the alterations in total lipid, AST, ALT, GSH and muscle glycogen. CONCLUSIONS: Our data suggest that F, T and M seeds powder supplementation may be beneficial for preventing diabetic complications in this animal model.

Protective and curative effects of the 15 KD isolated protein from the Peganum harmala L. seeds against carbon tetrachloride induced oxidative stress in brain, tests and erythrocytes of rats.

BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the protective and curative effects of the 15 KD protein isolated from the seeds of Peganum harmala L. against carbon tetrachloride (CCl4) induced oxidative stress in rats. MATERIALS AND METHODS: In the protective study, animals were pretreated intraperitoneally with 15 KD isolated protein at doses of 4 and 8 mg/kg body weight as well as vitamin C (250 mg/kg body weight p.o) for 7 days and then challenged with CCl4 orally (1 ml/kg body weight) in olive oil (50%) for 2 days. In the curative study, rats were administered CCl4 orally for 2 days, then treated intraperitoneally with 15 KD protein (4 and 8 mg/kg body weight) and orally with vitamin C. RESULTS: Administration of CCl4 induced induction in malondialdehyde (MDA) and decrease in reduced glutathione (GSH) levels as well as glutathione-S-transferase (GST) activity in brain, testes and erythrocytes. The activity of acetylcholinesterase (AchE) in brain was also inhibited by CCl4 administration. CONCLUSIONS: Treatment of rats either pre or post CCl4 intoxication successfully alleviated the oxidative stress in the brain, testes and erythrocytes of the experimental animals. Data also showed that the isolated protein possessed strong antioxidant activity comparable to that of vitamin C.

Clinical and immunomodulating effects of ketamine in horses with experimental endotoxemia.

BACKGROUND: Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs. HYPOTHESIS: Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses. ANIMALS: Nineteen healthy mares of various breeds. METHODS: Experimental study. Horses were randomized into 2 groups: ketamine-treated horses (KET; n = 9) and saline-treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor-α (TNF-α) and thromboxane B(2) (TXB(2)) were quantified. RESULTS: All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P < .05) and 1 hour after discontinuation of administration (P < .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P < .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF-α and TXB(2) production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated. CONCLUSIONS AND CLINICAL IMPORTANCE: A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF-α and TXB(2) production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.

2-(1,3-Benzothia-zol-2-yl)guanidin-2-ium acetate.

In the title compound, C(8)H(9)N(4)S(-)·C(2)H(3)O(2) (-), the cation is essentially planar (r.m.s deviation = 0.037 Å) with the guanidine unit bent out of the plane of the fused-ring system by 4.6 (3)°. In the asymmetric unit, the cations and anions are linked into R(2) (2)(8) motifs. In the crystal, further N-H⋯O and N-H⋯N hydrogen bonds link the components into a two-dimensional network.

Synthesis of a new antischistosomally active and toxicologically tolerant C-12 monothione surrogate of the universal antihelmintic praziquantel.

A new C-12 monothione mimic (III) of the universal antihelmintic Praziquantel (I) namely, 2-cyclohexylthiocarbonyl( 1,2.3,6,7,11b)-hexahydro-4H-pyrazino[2-1a] isoquinoline-4-one was chemically synthesized and structurally elucidated (Elemental analysis. El-Mass, 13C-NMR and IR spectroscopy). Antischistosomal potency in the order of -76% comparable to that for our newly reported C-12 and C-4 dithion mimic II (-70%) and Praziquantel. Praziquantel (100%, mice infected with S. mansoni cercariae), was realized. Toxicological evaluation (mice liver and kidney functions) and biochemical parameters (cholesterol, triglycerides, albumin, total serum proteins and amino acid profile of liver protein homogenate) were also assayed. Comparable to the parent drug, general insignificant toxicological diferences could be attributed for III. Interestingly, III exhibited intermediate biological figures between I and II. An order of IIIII>I, for the other tested biochemical parameters was observed. A consideration of obtained results could indicate that, structurally, an intact glycine amide segment of the pyrazine moiety, as it is the case in both I and III, and not in II (glycine thioamide) seemed now more crucial for exhibiting an optimum antihelmintic potency as well as a more tolerant toxicity characteristics. Additionally, the obtained comparable amino acid profile of mice liver protein homogenate after the treatment by III, could suggest similar biochemical, lethal mechanistic and metabolic routes for II, III and I. The new lipophilic candidatee III seems to merit more profound chemical, biological, and pharmaceutical investigations.

Changing trends in angioedema.

Angioedema can be a life-threatening event presenting to otolaryngologists, emergency medicine physicians, and other physicians. Recent reports suggest an increasing role of angiotensin-converting enzyme inhibitors (ACEIs) in the causation of angioedema. Sixty-four cases occurring between 1994 and 1998 were identified and examined retrospectively. Fifty-eight percent of patients presenting with angioedema were using ACEIs. Ninety-four percent of patients overall, and 92% of patients with ACEI-associated angioedema, were African-American. Tongue, lip, facial, and supraglottic edema were most common. Treatment included intubation in 13% and intensive care unit monitoring in 20%. Nearly all patients were treated with corticosteroids and antihistamines. There were no deaths. Angioedema associated with ACEI use appears to be much more common than previously reported. African-American patients may be at higher risk for angioedema with ACEI use. Successful management was achieved with observation, expectant airway management, corticosteroids, and discontinuation of ACEIs. Patients without airway obstruction or pharyngeal or laryngeal edema who improved with treatment and observation were successfully treated as outpatients.

Synthetic and bioorganic investigations of 2-cyclohexylthiocarbonyl( 1,2,3,6,7,11B)hexahydro-4H-pyrazino [2-1a] isoquinoline-4-thione, a new dithione mimic of the universal anthelminthic Praziquantel.

As a continuation for our previous approaches to establish structure-antischistosomal activity relationship (SAR) among some new rationally synthesized analogues of praziquantel, herein a new C-4 and C-12 dithione mimic of the drug namely, 2-cyclohexylthiocarbonyl (1, 2, 3, 6, 7, 11b) hexahydro-4H-pyrazino[2-la]isoquinoline-4-thione (II) was synthesized and antischistosomally investigated (mice infected with S. masoni cercariae). Further, some significant biochemical and toxicological parameters for both the control and the dithione II treated mice, particularly the total serum and liver proteins, liver enzymes, serum total lipids, cholesterol, triglycerides, albumin, globulins and creatinine, were assayed. The determined induced amino acid profile of liver protein hydrolysate could indicate a close similarity of the working biological mechanism for both I and II. Comparable to praziquantel, the dithione II was found, still promisingly antischistosomally active (approximately 70% of I, collective average activity, based on 500 mg II/kg mouse body weight). Equally, generally tolerant toxicity parameters for liver and kidney functions could be attributed. Due to the still absence of quasi-potent praziquantel candidates since its discovery (1975), the dithione II could be considered as an interesting anthelminthic candidate susceptible for further profound studies and structure modulations. In this context, some perspectives were also suggested.