Antiparasitic properties of homoallylamines and related compounds

A study of some antiparasitic properties of several homoallylamines and related tetrahydroquinolines and quinolines, previously described, was carried out using in vitro activity assays against the epimastigote form of Trypanosoma cruzi and against Trichomonas vaginalis. Unspecific cytotoxicity against murine macrophages was also studied. Although the antichagasic and trichomonacidal activities are not comparable to those of the standard drugs, nifurtimox and metronidazole, some of the compounds exhibit an interesting specific antiparasitic activity.     

Extraperitoneal endometriosis: a diagnosis to be considered

Summary BACKGROUND: Endometriosis is a relatively common pathology in women of childbearing age and of low parity but rarely shows extraperitoneal involvement. The main aim of this paper is to raise the attention of specialists to the necessity of carrying out penetrating diagnosis of nonspecific extraperitoneal masses occurring in women of reproductive age. METHODS: We performed a retrospective review of six patients diagnosed with extraperitoneal endometriosis who were treated at the Vega Baja University Hospital (Spain) during the last 5 years. RESULTS: Surgical treatment had positive results in five patients. The preoperative diagnosis was correctly made in only two patients. The accurate aetiology of endometriosis remains unknown and diagnosis is based on clinical and cytopathological findings. CONCLUSIONS: Surgical treatment of extraperitoneal endometriosis is recommended. However, postoperative follow-up is obligatory and hormonal suppressive therapy may be necessary. Medical treatment with gestagens, Danazol, or agonists of the gonadotropin-releasing hormone are ineffective in endometriomas which are bigger than 2 cm.      

Lipoprotein (a) levels in those with high molecular weight apo (a) isoforms may remain low in a significant proportion of patients with end-stage renal disease.

BACKGROUND: Studies have reported an increase in median Lipoprotein (Lp) (a) in patients with high molecular weight (HMW) apolipoprotein (apo) (a) isoforms and renal impairment. Some studies identify Lp (a) levels as a risk factor for vascular disease in renal failure whilst others have demonstrated an association with apo (a) isoform type and vascular disease. METHODS: A total of 239 patients at end-stage renal failure (ESRF) were studied prior to the initiation of dialysis. Blood was taken for Lp (a) levels and apo (a) isoforms. Clinical vascular disease (CVD) was assessed on the basis of clinical history and Rose questionnaire. The control group for Lp (a) levels consisted of 228 healthy volunteers. RESULTS: Despite a higher median Lp (a) level in those with HMW isoforms, 30% of patients had Lp (a) levels <10 mg/dl. Overall, 49% patients were identified as having CVD. Diabetes, smoking history and Lp (a) levels were significantly associated with CVD in logistic regression analysis, although when patients with low molecular weight (LMW) and HMW isoforms were analysed separately, Lp (a) levels were not significantly associated with CVD in those with LMW isoforms. The rates of CVD in those with HMW isoform and low Lp (a) levels were significantly lower than those with HMW isoforms and elevated Lp (a) levels, 34 vs 57% (P < 0.01). CONCLUSIONS: Although median Lp (a) levels in those patients at ESRF with HMW isoforms are higher than controls, in a third of such patients Lp (a) levels remain relatively low. These patients have lower rates of CVD than those with high levels of Lp (a).     

Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems.

In-situ forming drug delivery systems are prepared by dissolving a drug and a biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible organic solvent (In-situ implant, ISI) or further emulsified into an external phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA and the drug is a major concern. In this study, the stability of PLGA and leuprolide acetate in the in-situ forming systems and lyophilized sponges was investigated. The degradation of PLGA increased with increasing storage temperature and water content in the biocompatible solvents. A faster degradation occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl acetate). The presence of leuprolide acetate significantly accelerated PLGA degradation, especially in solution state. PLGA was stable in oily suspensions at 4 degrees C and degraded only slightly faster than solid powder at 25 degrees C. No interaction between the oils and the PLGA was observed as indicated by an unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4 degrees C after 150 days in water and saturated sodium chloride solution. The degradation was slower in saturated sodium chloride solution than in water at 25 degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA stability negatively. However, lidocaine significantly enhanced the polymer degradation in the sponges. Finally, leuprolide acetate was chemically stable in the sponges, the oils and the polymer solutions in suspension state, but unstable (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C and 40 degrees C.     

Multidisciplinary approach in the long-term management of intrahepatic stones: Indian experience.

BACKGROUND: Intrahepatic stones, though common in East Asia, are uncommon in India. There is paucity of data from India regarding the treatment and long-term outcome of patients with intrahepatic stones. METHODS: We retrospectively analyzed medical records of 35 patients with intrahepatic stones who had been treated surgically. Endoscopic biliary drainage had been used in patients who presented with acute cholangitis. Intraoperative stone clearance was confirmed by choledochoscopy and intraoperative cholangiography. Outcome of surgery, frequency and subsequent management of recurrent intrahepatic stones, and factors associated with stone recurrence and cholangitis were analyzed. RESULTS: Twenty-one (60%) patients had bilobar disease. Eight patients underwent hepatectomy and 16 hepatico-jejunostomy with access loop; 12 of these were jejuno-duodenal anastomoses. Postoperative morbidity was observed in 10 patients (29%). Recurrence of stones occurred in 12 patients (34%) and cholangitis in 9 patients (26%). Presence of bilobar disease and associated biliary strictures were associated with recurrent cholangitis (p< 0.05). Two patients (6%) required re-operation for recurrent cholangitis. Complete removal of recurrent stones using conventional endoscope was possible through jejuno-duodenostomy in all 5 cases who had this type of access loop construction. CONCLUSION: Surgical treatment for intrahepatic stones depends on the site of involvement. Construction of a jejuno-duodenal access loop in patients with bilobar disease and intrahepatic strictures is helpful in facilitating postoperative stone clearance. A multidisciplinary approach is beneficial especially when the disease is bilobar and recurrent in type.     

Biotransformation of organic substances by an immobilized associative bacterial culture]

Bacterial strains were screened to transform to end-products (carbon monoxide and water) elevated concentrations of acetone, acidic acid, and ethanol in a biocatalyst with an immobilized bacterial association cultivated on solid foam polyvinyl acetate (FPVA). The innocuous association amalgamated Paracoccus denitrificans VKM V-1324, Pseudomonas esterophilus VKM V-1736D and Achromobacter parvulus VKM V-1541D. The biocatalyst was tested with the help of classic methods and equipment for microbes cultivation. Microbial growth was assessed in the optical density units. Comparative evaluation of the biocatalytic activity was performed on gas-chromatographer Pue Unicam-104. Based on test results, specific rates of oxidation of acidic acid, ethanol and acetone per one g of FPVA were 0.75, 0.72, and 0.67 mg/hr, respectively.     

Evaluation of specialized laparoscopic suturing and tying devices.

BACKGROUND: Laparoscopic suturing and tying constitute advanced minimally invasive surgery skills. Developing proficiency in the standard methods with needle drivers is often an arduous process. Recent advances in laparoscopic instrumentations has allowed for easier methods of suturing and tying. This study investigated the hypothesis that the use of a specialized suturing device and a specialized tying device allows inexperienced medical students to suture and tie laparoscopically. METHODS: Preclinical medical students who had not received any training in open or laparoscopic surgery were included in this investigation. Each student was given a 5-minute demonstration of a specialized suturing device and a specialized tying device. The medical students were not allowed to deploy either device before actual use. After the demonstration, each student was given the device to use in a porcine model. Times were recorded and a subjective grade was given for each student. RESULTS: Twenty medical students were involved in this study. All medical students were able to complete the task of suturing and tying. The average time to suture was 104.6 seconds and the average time to tying was 31.2 seconds. The average subjective performance grade was 90 (out of 100). CONCLUSION: Specialized devices are easy to learn and use for laparoscopic suturing and tying with minimal instruction even for inexperienced medical students. Even surgeons who are not well versed in laparoscopic surgery should be able to suture and tie with certain laparoscopic instruments.     

Selective Postsynaptic Inhibition of Tonic-firing Neurons in Substantia Gelatinosa by μ-Opioid Agonist

Background: Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of [mu]-opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties.

Methods: Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO.

Results: Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 [mu]m concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K+ conductance, which could be blocked by 500 [mu]m Ba2+ and 500 [mu]m Cs+ but increased by 50 [mu]m baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting.