Exploring the potentials of underutilized grain amaranth (Amaranthus spp.) along the value chain for food and nutrition security: A review.

The burden of malnutrition in Africa calls for deeper exploration of underutilized species which are rich in nutrients and have the potential to reduce food and nutrition insecurity. The common staple crops are not able to meet daily requirements for both macro- and micro-nutrients. In order to lessen this burden; protein, calorie and micronutrient deficiencies must be properly addressed for optimal growth and development to be attained. African indigenous underutilized vegetables can play a significant role in the food security of vulnerable groups like under-five children and women in both urban and rural settings. The potential of grain amaranth in meeting the nutrition needs of humans has remained a subject of interest in scientific research. Amaranth is considered one of the most commonly produced and consumed indigenous vegetables on the African continent with high nutritional potentials but yet to be fully exploited. This review therefore aims at discussing the current knowledge of the inherent potentials of grain amaranths, its current application in the food industry and proposes a framework for actions and partnerships required to scale up and improve amaranth value chain.

Feeding practices of pre-school children and associated factors in Kathmandu, Nepal.

BACKGROUND: In developing countries such as Nepal, many children aged below 3 years do not grow at a sufficiently high rate and are vulnerable to micronutrient deficiencies (e.g. vitamin A). Challenges to child nutrition can result from poverty, unhealthy traditional practices, inadequate caring and feeding practices. The present study aimed to assess the feeding practices of pre-school children and their associated factors. METHODS: A cross-sectional study was carried out in pre-schools located in Kathmandu district between February and March 2018. Three levels in terms of price range (lower, medium and higher level) of pre-schools were selected to reach the mothers of children aged ≤3 years. A structured questionnaire was administered to 145 mothers. Descriptive analyses were conducted to observe the characteristics of the population. Multinomial logistic regression analyses were performed to identify the association for the factors of mothers' perception of their current feeding practices. RESULTS: We found that dal-bhat/jaulo was a common complementary food irrespective of socio-economic background. Interestingly, mothers who had received a higher education were significantly less likely to change their feeding practices (odds ratio = 0.118, confidence interval = 0.01-0.94). The mothers that fed a higher quantity porridge to their children showed a high willingness to change the feeding practices. CONCLUSIONS: Poor feeding practices are still an important public health problem in Nepal and were observed to be associated with low socio-economic status, unawareness and a lack of knowledge towards dietary diversity combined with strong beliefs related to social forces and cultures.

Pseudorheumatoid nodule: a variant of granuloma annulare?

We present an adult woman with subcutaneous nodules without any signs or symptoms of rheumatoid arthritis. These nodules are believed to be pseudorheumatoid nodules, which are considered a deep form of granuloma annulare. This case is unique because these are typically found in children and have rarely been reported in adults. These nodules are typically asymptomatic and do not require treatment. However, attempts have been made to treat them with intralesional corticosteroids, cryotherapy, or excision. Owing to the fact that this is considered a deep form of granuloma annulare, they are sometimes treated similarly with a combination of monthly rifampin, ofloxacin, and minocycline.

Nimbus-7 coastal zone color scanner: system description and initial imagery.

The Coastal Zone Color Scanner (CZCS) on Nimbus-7, launched in October 1978, is the only sensor in orbit that is specifically designed to study living marine resources. The initial imagery confirms that CZCS data can be processed to a level that reveals subtle variations in the concentration of phytoplankton pigments. This development has potential applications for the study of large-scale patchiness in phytoplankton distributions, the evolution of spring blooms, water mass boundaries, and mesoscale circulation patterns.

Dissolved oxygen as a key parameter to aerobic granule formation.

Much research has asserted that high shear forces are necessary for the formation of aerobic granular sludge in Sequencing Batch Reactors (SBRs). In order to distinguish the role of shear and dissolved oxygen on granule formation, two separate experiments were conducted with three bench-scale SBRs. In the first experiment, an SBR was operated with five sequentially decreasing superficial upflow gas velocities ranging from 1.2 to 0.4 cm s(-1). When less than 1 cm s(-1) shear was applied to the reactor, aerobic granules disintegrated into flocs, with corresponding increases in SVI and effluent suspended solids. However, the dissolved oxygen also decreased from 8 mg L(-1) to 5 mg L(-1), affecting the Feast/Famine regime in the SBR and the substrate removal kinetics. A second experiment operated two SBRs with an identical shear force of 1.2 cm s(-1), but two dissolved oxygen concentrations. Even when supplied a high shear force, aerobic granules could not form at a dissolved oxygen less than 5 mg L(-1), with a Static Fill. These results indicate that the substrate removal kinetics and dissolved oxygen are more significant to granule formation than shear force.

A new approach for categorizing pig lying behaviour based on a Delaunay triangulation method.

Machine vision-based monitoring of pig lying behaviour is a fast and non-intrusive approach that could be used to improve animal health and welfare. Four pens with 22 pigs in each were selected at a commercial pig farm and monitored for 15 days using top view cameras. Three thermal categories were selected relative to room setpoint temperature. An image processing technique based on Delaunay triangulation (DT) was utilized. Different lying patterns (close, normal and far) were defined regarding the perimeter of each DT triangle and the percentages of each lying pattern were obtained in each thermal category. A method using a multilayer perceptron (MLP) neural network, to automatically classify group lying behaviour of pigs into three thermal categories, was developed and tested for its feasibility. The DT features (mean value of perimeters, maximum and minimum length of sides of triangles) were calculated as inputs for the MLP classifier. The network was trained, validated and tested and the results revealed that MLP could classify lying features into the three thermal categories with high overall accuracy (95.6%). The technique indicates that a combination of image processing, MLP classification and mathematical modelling can be used as a precise method for quantifying pig lying behaviour in welfare investigations.

The influence of gallium and other metal ions on the uptake of non-transferrin-bound iron by rat hepatocytes.

BACKGROUND: Under conditions of iron overload non-transferrin-bound iron (NTBI) occurs in the circulation and is mainly cleared by the liver. Beside iron, gallium and aluminum enhance accumulation of NTBI. We try to characterize the mechanism and metal-mediated regulation of NTBI uptake using cultivated primary rat hepatocytes. METHODS: Hepatocytes from rat liver were incubated with 0.1 mg/ml transferrin (as control), with ferric ammonium citrate or other di- and trivalent metal salts and the uptake of (55)Fe-labeled Fe-diethylene triammine pentaacetate was measured. RESULTS: Uptake rates for iron increased from 0.3 to 2.1 pmol/mg protein per min in cells preincubated for 5 hours with 300 microM ferric ammonium citrate, to 1.7 pmol/mg protein per min with gallium and to 1.2 pmol/mg protein per min with aluminum. Maximal stimulation was obtained with 300 microM iron and 600 microM gallium. Preincubation with divalent metals was ineffective. NTBI uptake was specific for iron, partly inhibited by gallium citrate, diferric transferrin and completely inhibited by apotransferrin in control and gallium-treated cells. In iron-loaded cells, inhibition of NTBI uptake by diferric transferrin completely disappeared within 2 hours. CONCLUSIONS: These experiments show that hepatocytes do respond to the presence of trivalent metals by an increased transport capacity to sequester these ions. The metals seem to have at least partly different mechanisms of transport stimulation.

Prognostic evaluation of neurohumoral plasma levels before and during beta-blocker therapy in advanced left ventricular dysfunction.

OBJECTIVES: The study assessed the relative predictive potency of neurohumoral factors in patients with advanced left ventricular (LV) dysfunction during neurohumoral blocking therapy. BACKGROUND: The course of heart failure is characterized by progressive LV deterioration associated with an increase in cardiac (natriuretic peptides) and predominantly extracardiac (norepinephrine, big endothelin [big ET]) hormone plasma levels. METHODS: Plasma hormones were measured at baseline and months 3, 6, 12 and 24 in 91 patients with heart failure (left ventricular ejection fraction [LVEF] <25%) receiving 40 mg enalapril/day and double-blind atenolol (50 to 100 mg/day) or placebo. After the double-blind study phase, patients were followed up to four years. Stepwise multivariate regression analyses were performed with 10 variables (age, etiology, LVEF, symptom class, atenolol/placebo, norepinephrine, big ET, log aminoterminal atrial natriuretic peptide, log aminoterminal B-type natriuretic peptide [N-BNP] and log B-type natriuretic peptide [BNP]). During the study, the last values prior to patient death were used, and in survivors the last hormone level, New York Heart Association class and LVEF at month 24 were used. RESULTS: Thirty-one patients died from a cardiovascular cause during follow-up. At baseline, log BNP plasma level (x2 = 13.9, p = 0.0002), treatment allocation (x2 = 9.5, p = 0.002) and LVEF (x2 = 5.6, p = 0.017) were independently related to mortality. During the study, log BNP plasma level (x2 = 21.3, p = 0.0001) remained the strongest predictive marker, with LVEF (x2 = 11.2, p = 0.0008) log N-BNP plasma level (x2 = 8.9, p = 0.0027) and treatment allocation (x2 = 6.4, p = 0.0109) providing additional independent information. CONCLUSIONS: In patients with advanced LV dysfunction receiving high-dose angiotensin-converting enzyme inhibitors and beta-blocker therapy BNP and N-BNP plasma levels are both independently related to mortality. This observation highlights the importance of these hormones and implies that they will likely emerge as a very useful blood test for detection of the progression of heart failure, even in the face of neurohumoral blocking therapy.

Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure.

OBJECTIVES: We tested the hypothesis that, in patients with stable heart failure, measuring big endothelin-1 (ET-1) plasma level at rest predicts short-term prognosis better than peak oxygen consumption (VO2max) at exercise. BACKGROUND: Cardiopulmonary exercise testing and evaluation of neurohumoral plasma factors are established tools to estimate survival in patients with heart failure. No data, however, exist comparing the prognostic value of both marker categories simultaneously. METHODS: Two hundred twenty-six heart failure patients were studied in regard to a combined end point of death and prioritization for urgent cardiac transplantation within 1 year follow-up. RESULTS: During the study period 149 patients were without cardiac events (group A), 69 patients died or were urgently transplanted (group B) and 8 patients were alive after a nonurgent heart transplant operation. Norepinephrine (p < 0.0001), atrial natriuretic peptide (p < 0.001), big endothelin plasma levels (p < 0.0001 as well as workload, VO2max and achieved percentage of predicted peak oxygen consumption (pVO2max) (all p < 0.0001) differed significantly between groups A and B. In multivariate stepwise regression analysis, however, only big ET-1 plasma concentration (chi2=74.4, p < 0.0001), New York Heart Association function class (chi2=33.9, p < 0.0001), maximal workload (chi2=7.2, p < 0.01, and plasma atrial natriuretic peptide (ANP) concentration (chi2=4.6, p < 0.05) were independently related to outcome. Peak oxygen consumption or pVO2max did not reach statistical significance in this model. Event-free survival rates were significantly lower in patients with a big ET-1 level of 4.3 fmol/ml or more than with lower big ET-1 levels (p < 0.0001). CONCLUSION: We conclude that in patients with chronic heart failure who are stable on oral therapy measuring big ET-1 and ANP plasma levels may be a valuable noninvasive adjunct to improve the prognostic accuracy of detecting high risk patients compared with exercise testing alone.

Regional heterogeneity of function in nonischemic dilated cardiomyopathy.

OBJECTIVE: To quantify regional three-dimensional (3D) motion and myocardial strain using magnetic resonance (MR) tissue tagging in patients with non-ischemic dilated cardiomyopathy (DCM). METHODS: MR grid tagged images were obtained in multiple short- and long-axis planes in thirteen DCM patients. Regional 3D displacements and strains were calculated with the aid of a finite element model. Five of the patients were also imaged after LV volume reduction by partial left ventriculectomy (PLV), combined with mitral and tricuspid valve repair. RESULTS: DCM patients showed consistent, marked regional heterogeneity. Systolic lengthening occurred in the septum in both circumferential (%S(C) -5+/-7%) and longitudinal (%S(L) -2+/-5%) shortening components (negative values indicating lengthening). In contrast, the lateral wall showed relatively normal systolic shortening (%S(C) 12+/-6% and %S(L) 6+/-5%, P<0.001 lateral vs. septal walls). A geometric estimate of regional stress was correlated with shortening on a regional basis, but could not account for the differences in shortening between regions. In the five patients imaged post-PLV, septal function recovered (%S(C) 9+/-5%,%S(L) 6+/-5%, P<0.02 pre vs. post) with normalization of wall stress, whereas lateral wall shortening was reduced (%S(C) 7+/-6%,%S(L) 3+/-3%, P<0.02 pre vs. post) around the site of surgical resection. CONCLUSIONS: A consistent pattern of regional heterogeneity of myocardial strain was seen in all patients. Reduced function may be related to increased wall stress, since recovery of septal function is possible after PLV. However, simple geometric stress determinants are not sufficient to explain the functional heterogeneity observed.

Synthesis of some 3-(1-azabicyclo[2.2.2]octyl) 3-amino-2-hydroxy-2-phenylpropionates: profile of antimuscarinic efficacy and selectivity.

A series of 3-quinuclidinyl atrolactate [3-(1-azabicyclo[2.2.2]octyl) 2-hydroxy-2-phenylpropionate, QNA] derivatives in which the methyl group of the parent is substituted with a tertiary amino substituent was prepared and tested for antimuscarinic activity. In general, potency was markedly decreased, although the morpholinyl and thiomorpholinyl derivatives retained significant activity. These compounds were also examined for muscarinic receptor subtype selectivity. Their subtype selectivities were comparable to that of (R,R)-QNA. The results of this investigation suggest possible differences in the accessory binding sites of the proteinaceous receptor subtypes.

Synthesis and antimuscarinic properties of some N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones.

In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)-3,3-diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H-imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H )- furanone (23) as a clinical candidate for treating urinary bladder dysfunction.

Effect of beta 1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril.

BACKGROUND: The survival benefit of beta-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of beta-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported. AIMS: To investigate the effect of atenolol, a hydrophilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial. METHODS: One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction < or = 25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12. 5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89+/-11 mg/day, range 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events. RESULTS: After 395+/-266 days interim analysis revealed a significant difference between the atenolol and placebo group (log rank P<0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P=0.05) and 10 due to arrhythmias (1 in the atenolol group vs. 9 in the placebo group, P<0.01) CONCLUSIONS: The data suggest that in patients with advanced left ventricular dysfunction, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.

Response of right ventricular function to prostaglandin E1 infusion predicts outcome for severe chronic heart failure patients awaiting urgent transplantation.

BACKGROUND: Selection of patients for urgent heart transplantation who have end-stage heart failure requires objective criteria to distinguish between subjects who may deteriorate clinically and those who can be stabilized. This population appears to differ in terms of right ventricular function, and right ventricular changes in loading may provide prognostic information. To investigate predictive parameters of patients admitted for urgent heart transplantation, we prospectively studied the mechanical performance of the right ventricle during acute afterload reduction. PATIENTS AND METHODS: We studied 68 heart failure patients hospitalized for bridge-to-transplant. The patients underwent right heart catherization at baseline and during prostaglandin E1 infusion. We stratified patients according to clinical outcome: Group A comprised patients who could be weaned from bridging therapy or who were electively transplanted after at least 90 days, and Group B comprised patients who died or who remained unstable and required transplant under urgent conditions. RESULTS: Right ventricular hemodynamics at baseline were comparable in both groups. However, during maximal vasodilatation, with prostaglandin E1 infusion, the right ventricular end-diastolic volume index (EDVI) was significantly reduced in Group A, (-23 ml/m(2) (p < 0.01) vs +12 ml/m(2) (p = n.s. DeltaEDVI in Group B. Reduction of EDVI by less than 10% during prostaglandin E1 infusion has a sensitivity of 89% and a specificity of 70% for clinical deterioration. CONCLUSIONS: The response of right ventricular volumes to prostaglandin E1 may predict the outcome of patients with severe congestive heart failure listed for urgent heart transplantation.

Long-term effect of atenolol on ejection fraction, symptoms, and exercise variables in patients with advanced left ventricular dysfunction.

AIMS: We recently reported a beneficial clinical effect of atenolol, a beta(1) selective adrenergic antagonist, in 100 ambulatory heart failure patients with low left ventricular ejection fraction (LVEF,

Bridging to heart transplantation: prostaglandin E1 versus prostacyclin versus dobutamine.

BACKGROUND: Prostaglandin E1 (PGE1) and prostacyclin have potent pulmonary and systemic vasodilating properties. This prospective, randomized trial compared PGE1 vs prostacyclin vs. low-dose dobutamine in patients with low-output heart failure awaiting heart transplantation (HTx) who were refractory to oral treatment. METHODS: Patients in advanced heart failure in New York Heart Association (NYHA) Class IV, with a cardiac index < or = 2.5 L/minute/m2 and a pulmonary capillary wedge pressure > or = 20 mmHg, who were listed for HTx were studied. In an inpatient study phase of 12 hours duration, therapy was aimed to increase cardiac output by 20% or more, when compared to baseline values, and to achieve a reduction of pulmonary vascular resistance below 550 dyn.s/cm-5m-2. During a long-term outpatient phase, the drugs were continuously infused to bridge these patients to HTx using three combined negative endpoints (worsening heart failure, serious adverse events, death) for analysis. RESULTS: Sixty-eight patients were enrolled, 30 patients on PGE1, 8 patients on prostacyclin, and 30 patients on dobutamine. During the inpatient study phase, maximum doses were 22 +/- 1.8 ng/kg/minute for PGE1, 7 +/- 1 ng/kg/minute for prostacyclin and 5 +/- 0.4 micrograms/kg/minute for dobutamine. During the inpatient study phase 21 patients failed, 4/30 (13%) patients on PGE1, 4/8 patients on prostacyclin (50%), and 13/30 (43%) on dobutamine (p < 0.05). Long-term continuous intravenous drug infusion in outpatients was begun in 26 patients on PGE1, in 4 patients on prostacyclin, and in 17 patients on dobutamine. Infusion therapy lasted for 88 +/- 14 days in the PGE1 group with 31 +/- 22 days in the prostacyclin group, and 30 +/- 8 days in the dobutamine group (NS). During the outpatient phase 23 patients reached a negative endpoint with 16 patients developing worsening heart failure, 5 severe adverse events and 2 deaths. Seven out of 26 (27%) failed on PGE1, 4/4 (100%) failed on prostacyclin, and 12/17 (71%) failed on dobutamine (p < 0.05, log rank test). Because prostacyclin treatment was ineffective in the first 8 patients, this trial arm was stopped prematurely. CONCLUSIONS: The findings from this prospective open pilot trial suggest that continuous PGE1 infusions at individualized dosages can be useful in certain patients as a pharmacologic bridging procedure with reduced risk to develop worsening heart failure before HTx compared to prostacyclin and dobutamine. Further comparative studies are warranted to investigate the effects of PGE1 among other bridging agents.

Stereoselective antimuscarinic effects of 3-quinuclidinyl atrolactate and 3-quinuclidinyl xanthene-9-carboxylate.

The relative affinity and selectivity of the stereoisomers of 3-quinuclidinyl atrolactate (QNA) and the enantiomers of 3-quinuclidinyl xanthene-9-carboxylate (QNX) for the pharmacologically defined muscarinic receptor subtypes was determined using functional responses of rabbit vas deferens (M1), guinea pig atria (M2) and bladder detrusor muscle (M3). All the stereoisomers behaved as competitive antagonists yielding the same rank order of potency at each receptor subtype: (RR)-QNA greater than (RS)-QNA greater than (SR)-QNA greater than (SS)-QNA and (R)-QNX greater than (S)-QNX. Moreover, the eudismic ratios relative to (RR)-QNA for (RS)-, (SR)- and (SS)-QNA, respectively, ranged from 4 to 308 at all three subtypes. Stereoselective effects were also observed for QNX; (S)-QNX/(R)-QNX ratios ranged from 76 to 248. In contrast, there was a distinct lack of receptor selectivity among the isomers of QNA and QNX for either the M1, M2 or M3 muscarinic receptor subtypes. Stereoselective effects were also evident in vivo in the guinea pig cystometrogram, where the rank order of potency of the isomers of QNA and QNX was similar to that observed in vitro. (RR)-QNA and (R)-QNX equipotently depressed intravesical bladder pressure (PvesP) (ID50 = 0.06 mg/kg i.v.). Other parameters (bladder capacity, threshold pressure) were unaltered by the stereoisomers. The data demonstrate that despite the high affinity of the eutomers of QNA and QNX for muscarinic receptors, they discriminate poorly among muscarinic subpopulations, thus limiting their utility to subclassify muscarinic receptors.

(+/-)-Terodiline: an M1-selective muscarinic receptor antagonist. In vivo effects at muscarinic receptors mediating urinary bladder contraction, mydriasis and salivary secretion.

The affinity and selectivity of racemic terodiline (N-tert-butyl-1-methyl-3,3-diphenylpropylamine HCl) for muscarinic receptor subtypes was determined from functional responses of rabbit vas deferens (M1), guinea pig atria (M2) and bladder detrusor muscle (M3). (+/-)-Terodiline was found to be about as potent as pirenzepine in the rabbit vas deferens (Kb = 15 and 31 nM, respectively) and at least as selective for M1 relative to M2 (11-fold) and M3 (19-fold) receptors. Like pirenzepine, (+/-)-terodiline does not distinguish between M2 and M3 receptors in vitro. The peripheral actions of (+/-)-terodiline were evaluated in vivo in terms of its ability to induce mydriasis, and to inhibit salivary secretion and urinary bladder contraction. (+/-)-Terodiline given s.c. was equipotent in inhibiting intravesical bladder pressure and carbachol-induced salivary secretion (ID50 = 24 and 35 mg/kg, respectively), and in increasing pupil diameter (ED50 = 59 mg/kg). These results suggest that the in vivo actions of racemic terodiline at (M3) receptors mediating bladder contraction may not be separable from its actions at receptors mediating mydriasis and salivation. Moreover, its effects on the pupil and salivary glands are apparently not mediated through M1 receptors. Together, these findings help clarify the action of (+/-)-terodiline in the treatment of neurogenic bladder.

In vitro and in vivo antimuscarinic effects of (-)cis 2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5 benzothiazepin-4-(5H)one HCl (BTM-1086) in guinea pig peripheral tissues.

The potency and selectivity of (-)cis-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5 benzothiazepin-4-(5H)one HCl (BTM-1086) for muscarinic receptor subtypes was compared in functional assay systems, in guinea pig peripheral tissues, to known reference drugs: atropine (nonselective), pirenzepine (M1), AF-DX 116 (M2) and HHSiD (M3). Like atropine, BTM-1086 was a potent, nonselective, competitive muscarinic antagonist with no detectable antispasmodic activity in urinary bladder or ileal muscle. In vivo, in the guinea pig cystometrogram, BTM-1086 depressed intravesical bladder pressure (PvesP) with the same efficacy and potency as oxybutynin, a drug used clinically for the treatment of urinary incontinence. The pharmacological profile of BTM-1086, however, suggests that it may not be suitable for development for bladder dysfunction disorders.

Estimation of current leakage in left and right ventricular conductance volumetry using a dynamic finite element model.

Leakage of electric current through cardiac structures surrounding the ventricle is a primary source of error during ventricular volume measurements using a conductance catheter. This error can be represented as a leakage volume, VL. VL is generally estimated by a saline-bolus method, and is assumed constant throughout the cardiac cycle. However, dynamic changes in ventricular volume and cardiac wall thickness could change VL. To estimate VL, a dynamic finite element model of the heart was developed based on MR images. Conductance measurements were simulated using a modeled conductance catheter, and true VL was calculated. VL varied from 22.7 ml (end-systole) to 26.4 ml (end-diastole) in the left ventricle and from 19.9 ml (end-systole) to 26.9 ml (end-diastole) in the right ventricle. The saline-bolus method underestimated VL in both the left (VL = 19.4 ml) and the right (VL = 4.1 ml) ventricular volume measurements. VL increased linearly with the ratio of blood to tissue resistivity, and changed minimally with catheter position. These results indicate that VL has to be estimated dynamically throughout the cardiac cycle to obtain accurate cardiac volume measurements. The results also show that the saline bolus method does not estimate current leakage accurately, especially in the right ventricular volume measurement.