The prophylactic and therapeutic impact of Trichinella spiralis larvae excretory secretory antigens- loaded Ca-BTC metal organic frameworks on induced murine colitis.

Background: Inflammatory bowel disease is an autoimmune disease that affects the gut. T. spiralis larvae (E/S Ags) loaded on calcium-benzene-1,3,5-tricarboxylate metal-organic frameworks (Ca-BTC MOFs) were tested to determine whether they might prevent or cure acetic acid-induced murine colitis. Methods: T. spiralis larvae E/S Ags/Ca-BTC MOFs were used in prophylactic and therapeutic groups to either precede or follow the development of murine colitis. On the seventh day after colitis, mice were slaughtered. The effect of our target antigens on the progress of the colitis was evaluated using a variety of measures, including survival rate, disease activity index, colon weight/bodyweight, colon weight/length) ratios, and ratings for macroscopic and microscopic colon damage. The levels of inflammatory cytokines (interferon-γ and interleukin-4), oxidative stress marker malondialdehyde, and glutathione peroxidase in serum samples were evaluated. Foxp3 T-reg expression was carried out in colonic and splenic tissues. Results: T. spiralis larvae E/S Ags/Ca-BTC MOFs were the most effective in alleviating severe inflammation in murine colitis. The survival rate, disease activity index score, colon weight/length and colon weight/bodyweight ratios, and gross and microscopic colon damage scores have all considerably improved. A large decrease in proinflammatory cytokine (interferon-γ) and oxidative stress marker (malondialdehyde) expression and a significant increase in interleukin-4 and glutathione peroxidase expression were obtained. The expression of Foxp3+ Treg cells was elevated in colonic and splenic tissues. Conclusion: T. spiralis larvae E/S Ags/Ca-BTC MOFs had the highest anti-inflammatory, antioxidant, and cytoprotective capabilities against murine colitis and might be used to develop new preventative and treatment strategies.

Efficacy of neuromuscular electrical stimulation of calf muscles on nocturnal symptoms and quality of life in asthmatic children.

OBJECTIVE: To determine whether neuromuscular electrical stimulation of calf muscles could improve nocturnal symptoms and quality of life in asthmatic children. PATIENTS AND METHODS: Sixty children (8-12 years) with moderate asthma were randomly allocated to three groups (A, B, and C). The three groups completed 12 weeks of supervised breathing exercises for 30 min. In addition, group A completed neuromuscular electrical stimulation of the calf muscles and group B completed aerobic exercise in the same period. The intervention was conducted five days a week for 12 consecutive weeks. Pre-and post-treatment evaluations involved pulmonary function tests, the Children's Asthma Control Questionnaire, calf muscle isometric muscle force, six-minute walk test, and Pediatric Asthma Quality of Life Questionnaire. RESULTS: A significant increase in all measured variables was recorded in all groups in favor of group A (p < 0.001). However, calf muscle isometric muscle strength, and nocturnal symptoms were non-significant in group C (p > 0.05). There was a significant difference between groups A and C in all measured variables (p < 0.001) in favor of group A. Significant differences between groups B and C in all measured variables (p < 0.001) in favor of group B were also noted. No significant differences were seen between groups A and B (p > 0.05). CONCLUSIONS: Neuromuscular electrical stimulation of calf muscles is an excellent adjunct to breathing exercise programs in improving nocturnal symptoms and quality of life in asthmatic children. Moreover, it can serve as a considerable alternative to traditional physical training in periods of disease exacerbation.

Effect of aerobic exercise on inflammatory markers in polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). In this regard, the present study examined the potential effects of aerobic exercise on interleukin-6 (IL6), tumor necrosis factor (TNF), and C-reactive protein (CRP) in PCOS women. PATIENTS AND METHODS: This was a randomized clinical trial that included 40 females aged 25-35 years diagnosed with PCOS. The participants were divided into two groups equal in number: the aerobic exercise group (AEM), and the metformin group (M). The AEM group performed aerobic exercise three times a week for 12 weeks in addition to metformin treatment. The M group received metformin only. Participants were assessed for IL-6, TNF-α, and CRP at baseline and after 12 weeks of intervention. RESULTS: The findings showed a significant reduction in IL-6, TNF-α, and CRP values in both AEM and M groups (p=0.001, p=0.01, respectively) after the end of the 12 weeks of the intervention. However, the participants who received aerobic exercise plus metformin, group AEM, showed a greater reduction in IL-6, TNF-α, and CRP (p=0.01, p = 0.01 and p=0.001, respectively). CONCLUSIONS: Aerobic exercise is effective in lowering IL-6, TNF-α, and CRP in polycystic ovarian women. Further clinical trials are recommended to assess the potential effects of aerobic exercise on PCOS-associated risk factors.

Efficacy of different approaches on quality of upper extremity function, dexterity and grip strength in hemiplegic children: a randomized controlled study.

OBJECTIVE: To investigate the effect of mirror therapy (MT) together with taping compared to modified constraint-induced movement therapy (mCIMT) and MT alone on the quality of upper extremity (UE) function, dexterity, and grip strength in children with hemiplegic cerebral palsy (CP). PATIENTS AND METHODS: Sixty children with hemiplegic CP ranging in age from 6 to 8 years were enrolled. The participants were randomly distributed into three groups. The three groups underwent the same suggested upper limb (UL) exercise programme for 1h/5 days/week for 12 successive weeks. Group A performed the programme with MT and taping. Group B performed the same programme using mCIMT alone, while group C performed this programme with MT alone. In addition, the three groups underwent a routine physical therapy programme for 1 h. The quality of UE function, dexterity, and grip strength was measured using the Quality of Upper Extremity Skills Test (QUEST), Box and Block Test (BBT), and hand-held dynamometer before and after 12 successive weeks of treatment. RESULTS: After treatment, the measurement of all variables in the three groups showed significant improvements with superior effects seen in group A. CONCLUSIONS: Based on the results obtained in this study, MT with taping, mCIMT alone, and MT alone are good supplements to traditional physical therapy programmes in improving the quality of UE function, dexterity, and grip strength in children with hemiplegic CP with more superior effects seen after using MT together with taping.

Impact of Schroth three-dimensional vs. proprioceptive neuromuscular facilitation techniques in adolescent idiopathic scoliosis: a randomized controlled study.

OBJECTIVE: The aim of the study was to investigate the effect of proprioceptive neuromuscular facilitation (PNF) and compare its effect to the Schroth exercises on scoliosis angle, static plantar pressure distribution, and functional capacity in adolescent idiopathic scoliosis. PATIENTS AND METHODS: Thirty-four girls (aged 14-16 years) with thoracolumbar curves were randomly distributed into two study groups of equal numbers. The Schroth group underwent Schroth exercises, whereas the PNF group underwent treatment using proprioceptive neuromuscular facilitation. Patients in both groups received treatment for one hour, three times per week for six successive months. Measurements of Cobb's angle, angle trunk rotation, total static plantar pressure on both lower limbs, and functional capacity using the six-minute walk test were performed just before and after six months of treatment. RESULTS: A significant decrease in Cobb's angle and right total static plantar pressure with a significant increase in left total static plantar pressure post-treatment was noted in both groups, with a higher effect in the Schroth group. A significant increase was recorded in the six-minute walk test with a decrease in angle trunk rotation in the Schroth group, while no significant changes were recorded in the PNF group. CONCLUSIONS: Based on the results obtained in this study, this program of PNF patterns did not show a significant improvement in angle trunk rotation, which is a critical aspect in correction of the curve in comparison to the Schroth exercises. These proprioceptive neuromuscular facilitation patterns are not recommended for the correction of adolescent idiopathic scoliosis.

Bifurcation analysis of a network-based SIR epidemic model with saturated treatment function.

In this paper, we present a study on a network-based susceptible-infected-recovered (SIR) epidemic model with a saturated treatment function. It is well known that treatment can have a specific effect on the spread of epidemics, and due to the limited resources of treatment, the number of patients during severe disease outbreaks who need to be treated may exceed the treatment capacity. Consequently, the number of patients who receive treatment will reach a saturation level. Thus, we incorporated a saturated treatment function into the model to characterize such a phenomenon. The dynamics of the present model is discussed in this paper. We first obtained a threshold value R0, which determines the stability of a disease-free equilibrium. Furthermore, we investigated the bifurcation behavior at R0=1. More specifically, we derived a condition that determines the direction of bifurcation at R0=1. If the direction is backward, then a stable disease-free equilibrium concurrently exists with a stable endemic equilibrium even though R0<1. Therefore, in this case, R0<1 is not sufficient to eradicate the disease from the population. However, if the direction is forward, we find that for a range of parameters, multiple equilibria could exist to the left and right of R0=1. In this case, the initial infectious invasion must be controlled to a lower level so that the disease dies out or approaches a lower endemic steady state.

Population pharmacokinetic analysis of clopidogrel in healthy Jordanian subjects with emphasis optimal sampling strategy.

AIM: Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel-IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM(®) to describe the time course of clopidogrel-IM in plasma and to design a sparse-sampling strategy to predict clopidogrel-IM exposures for use in characterizing anti-platelet activity. METHODS: Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel-IM using reverse phase high performance liquid chromatography. A two-compartment (2-CMT) PK model with first-order absorption and elimination plus an absorption lag-time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3-12 post-dose samples. RESULTS: A two-compartment model with EHC provided the best fit and reduced bias in C(max) (median prediction error (PE%) of 9.58% versus 12.2%) relative to the basic two-compartment model, AUC(0-24) was similar for both models (median PE% = 1.39%). The OSS for fitting the two-compartment model with EHC required the collection of seven samples (0.25, 1, 2, 4, 5, 6 and 12 h). Reasonably unbiased and precise exposures were obtained when re-fitting this model to a reduced dataset considering only these sampling times. CONCLUSIONS: A two-compartment model considering EHC best characterized the time course of clopidogrel-IM in plasma. Use of the suggested OSS will allow for the collection of fewer PK samples when assessing clopidogrel-IM exposures.

Growth performance of indigenous sheep fed Sporobolus virginicus grass hay grown in saline desert lands and irrigated with high salt content ground water.

Twenty-eight indigenous ewe lambs (6 months of age and 14.4 kg body weight (BW)) were used to evaluate the effect of feeding Sporobolus grass hay (SGH) as the only source of forage on growth, and feed and water intakes. The ewe lambs were randomly and equally allocated to two treatment groups (14 lambs/group). The ewe lambs in group 1 (treatment 1) received SGH, while lambs in group 2 (treatment 2) received Rhodes grass hay (RGH) as the only source of forage. Water was available at all times for both treatment groups. Sporobolus grass was irrigated with brackish water of high salt content (20,000 ppm) and grown in saline desert lands (sabkha) in the United Arab Emirates. The average daily dry matter intake was significantly (P < .05) higher for the animals fed SGH than those fed RGH at all stages. Both water intakes per unit body gain and water intake per unit feed intake were significant (P < .05) between the two treatments group at all stages. Average daily gain did not differ significantly (P > .05) between the two groups at all stages. From these data, we conclude that SGH can replace Rhodes hay in sheep diet without significant effect on sheep performance.

Triangle of safety technique: a new approach to laparoscopic cholecystectomy.

UNLABELLED: BACKGROUNDS AND STUDY AIMS: Common bile duct (CBD) injury is one of the most serious complications of laparoscopic cholecystectomy (LC). Misidentification of the CBD during dissection of the Calot's triangle can lead to such injuries. The aim of the authors in this study is to present a new safe triangle of dissection. PATIENTS AND METHOD: 501 patients under went LC in the following approach; The cystic artery is identified and mobilized from the gall bladder (GB) medial wall down towards the cystic duct which would simultaneously divide the medial GB peritoneal attachment. This is then followed by dividing the lateral peritoneal attachment. The GB will be unfolded and the borders of the triangle of safety (TST) are achieved: cystic artery medially, cystic duct laterally and the gallbladder wall superiorly. The floor of the triangle is then divided to delineate both cystic duct and artery in an area relatively far from CBD. RESULTS: There were little significant immediate or delayed complications. The mean operating time was 68 minutes, nearly equivalent to the conventional method. CONCLUSIONS: Dissection at TST appears to be a safe procedure which clearly demonstrates the cystic duct and may help to reduce the CBD injuries.

Smoking behaviour modulates pharmacokinetics of orally administered clopidogrel.

BACKGROUND AND OBJECTIVES: Clopidogrel is an important antiplatelet drug that is effective in preventing thrombotic events, especially for patients undergoing percutaneous coronary intervention. The therapeutic usefulness of clopidogrel has been limited by documented inter-individual heterogeneity in platelet inhibition, which may be attributable to known clopidogrel pharmacokinetic variability. The objective of this study was to assess the influence of smoking cigarettes and abnormal body weight on the pharmacokinetics of clopidogrel. METHODS: Seventy-six healthy adult male volunteers were selected randomly. Each subject received a single 75 mg oral dose of clopidogrel after overnight fast. Clopidogrel carboxylate plasma levels were measured and non-compartmental analysis was used to determine peak plasma concentration (C(max)), time to peak plasma concentration (T(max)), elimination half-life (t(1/2e)), and area under the curve (AUC(0-->infinity)). RESULTS: One-third of volunteers were smokers (n = 27) and one-half had abnormal body weight (n = 39). Smokers had lower AUC(0-->infinity) (smokers: 6.24 +/- 2.32 microg/h/mL vs. non-smokers: 8.93 +/- 3.80 microg/h/mL, P < 0.001) and shorter half-life (smokers: 5.46 +/- 2.99 vs. non-smokers: 8.43 +/- 4.26, P = 0.001). Smoking behaviour had no influence on C(max) (P = 0.3) and T(max) (P = 0.7). There was no statistically significant difference in C(max), AUC(0-->infinity), T(max) and t(1/2e) between volunteers with abnormal body weight and normal body weight. However the difference in body weight of the two groups was relatively narrow (mean +/- SE; 26.93 +/- 0.16 vs. 23.11 +/- 0.27). In general, the pharmacokinetic parameters were characterized by considerable inter-individual differences (C(max) = 3.09 +/- 0.99 microg/mL, CV = 32%), (T(max) =0.76 +/- 0.24 h, CV = 31.6%), (AUC(0-->infinity) = 7.98 +/- 3.58 microg/h/mL, CV = 44.8%), and (t(1/2e) = 7.38 +/- 4.10 h, CV = 55.6%). CONCLUSION: Smoking is a significant factor affecting the pharmacokinetics of clopidogrel, following administration of a single 75 mg dose in healthy young volunteers. The study supports smoking-cessation recommendations. Further studies are required to evaluate the influence of smoking and body weight on the pharmacokinetics of the active metabolite of clopidogrel and on the clinical effects of any differences observed.

An innovative pharmaceutical care practical course.

The innovative practical course was developed to improve the students' ability to acquire pharmaceutical care skills. The primary components of the course were in-school training using small group discussions and hospital experience including identification, analysis, prevention and resolution of drug-therapy problems, patient counseling on their medications and diseases, and interaction with medical team. Specific objectives of the research were to (1) compare students' performance before and after the course, (2) measure students' perceptions of their pharmaceutical care skills before and after the course, (3) determine students' perception of the value of the course. Statistical comparison of pre-test and post-test grades indicated both a retention and acquiring pharmaceutical care skills. A pre-course and post-course survey instrument was designed to measure students' perception of their pharmaceutical care skills. Perception of most of the items of the survey was significantly improved at the end of the course. Overall, the majority of students were highly satisfied with the course. In conclusion, the present study demonstrates that the innovative pharmaceutical care practical course was successfully introduced.

Structural analysis of cDNA encoding thymidylate synthase in hepatic metastases of human colorectal tumors.

The enzyme thymidylate synthase (TS) is an important target of 5-fluorouracil (FUra) that is utilized for the treatment of disseminated colorectal cancer. One determinant of clinical response to FUra-based therapy is TS expression. with high levels of expression being predictive of poor response. In the present investigation the levels of immunoreactive TS were analyzed in human colon metastases in the liver (n=l1). The levels of TS ranged from 0.30 to 4.60 pmol TS/g tissue. A good correlation was observed between the levels of immunoreactive TS and TS mRNA (n=6, r=0.69). Of the 11 metastases analyzed, 5 exhibited relatively high levels of TS expression. Two metastases with high TS expression were obtained from patients who received adjuvant therapy with FUra. In 4 metastases with relatively high levels of TS expression, TS gene copy number was analyzed. No evidence for amplification of TS gene sequences was observed. The basis for the high levels of TS expression was examined by structural analysis of TS cDNA. No nucleotide sequence differences were detected in the coding regions of the TS genes from the metastases. Mutations were detected at positions 961 and/or 1031 in the 3'-untranslated regions of the TS gene from the metastases; mutations at these sites were also detected in DNA isolated from normal colon mucosa (n=4) and primary colorectal tumors (n=4). No correlation was observed between TS expression and the nucleotide alterations at these positions. Polymorphism was observed in the 5'-untranslated regions of the TS gene in hepatic metastases (n=6). A general trend was observed between the structure of the 5'-untranslated region of the gene and TS expression.

Segmental analysis of SPECT 99mTc-methoxy isobutyl isonitrile and 201Tl myocardial imaging in ischaemic heart disease.

To study the potential usefulness of 99mTc-methoxy isobutyl isonitrile (99mTc-MIBI) as a substitute for 201Tl in assessing patients with ischaemic heart disease, 24 patients underwent 1 day rest and exercise 99mTc-MIBI single photon emission computerised tomography (SPECT) 1 week after SPECT exercise 201Tl. All patients were catheterized within 1 month after myocardial imaging. In 17 patients, resting first pass radionuclide angiography (FPRNA) was performed with 99mTc-MIBI. The heart to lung ratio for 99mTc-MIBI and 201Tl was calculated both at rest and exercise. The segmental analysis for myocardial perfusion reveals that 87/96 segments (91%) were correctly classified by SPECT 201Tl and 84/96 segments (88%) were correctly classified by 99mTc-MIBI. A significant correlation was present between LVEF measured by 99mTc-MIBI FPRNA and contrast ventriculography (r = 0.85, P less than 0.0001). The heart to lung ratio both at rest and exercise for 99mTc-MIBI is significantly higher than 201Tl (P less than 0.01 and less than 0.001 respectively). We conclude that 99mTc-MIBI is a promising agent for simultaneous evaluation of myocardial perfusion and cardiac function.

First derivative spectrophotometric determination of anhydrotetracyclines in tetracyclines.

A rapid method is presented for detection and determination of anhydrotetracycline-HCl (ATC-HCl) and 4-epianhydrotetracycline-HCl (4-EATC-HCl) in tetracycline-HCl (TC-HCl). The method determines the 2 compounds as a sum, not individually. The first derivative absorption curve has a trough (D1) at 460 nm which is linearly related to concentration (1-10 mg/mL). ATC-HCl + 4-EATC-HCl content was determined in TC-HCl powder and capsules by the D1 and the compensation D1 spectrophotometric methods. The results were compared with those obtained using U.S. Pharmacopeia and British Pharmacopoeia methods.

New nonsurgical technique for multiple pericardial biopsies.

We report a new, nonsurgical technique for obtaining multiple pericardial biopsies in patients with pericardial effusion. A short catheter is introduced by the Seldinger technique under fluoroscopy through the subxiphoid approach. The pericardial fluid is aspirated and the catheter replaced by an 8F teflon sheath with a curved tip. A bioptome is inserted through the sheath, and air is allowed to enter the pericardium. This method outlines the parietal percardium. The curved sheath directs the bioptome to the left or right wall. Eighteen consecutive patients had an average of eight pieces of pericardium removed. On histological examination, three patients had malignancy. Six had tuberculous granuloma, and mycobacterium tuberculosis was cultured from all six tissue specimens but only once from the fluid. Tissue smears showed acid fast bacilli in four out of six, whereas the fluid was negative in all. The biopsy yielded diagnostic information in nine out of ten patients with a thickened pericardium. There were no complications.

A comparison of two radionuclide ejection-fraction techniques with contrast angiography in ischemic heart disease and valvular heart disease.

First-pass radionuclide angiography (FPRA) in the 30 degree right anterior oblique and equilibrium gated radionuclide angiography (EGNA) in the 45 degree left anterior oblique were used for quantitative measurements of left ventricular ejection fraction (LVEF). Equipment used was a 400T gamma-camera interfaced with a Simis III Informatek computer. The results were compared with contrast angiography (CA). The aim of this study was to determine the sensitivity of both radionuclide techniques. The present data are based on 65 patients in whom CA and EGNA were performed. In 47 patients both FPRA and EGNA were performed. Results suggested that in ischemic heart disease (IHD) and valvular heart disease (VHD) the EGNA technique is well correlated with CA (r = 0.9 and 0.73, respectively). FPRA correlated well only with CA in IHD (r = 0.86), but not in VHD (r = 0.18). This study indicates that both FPRA and EGNA are sensitive, noninvasive techniques for measuring ejection fraction in IHD, while in VHD, EGNA is more sensitive technique than FPRA.