Transanal endoscopic surgery with a 3D printed device.

BACKGROUND: The aim of this study was to investigate the effectiveness of devices manufactured with 3D printing for performing transanal endoscopic procedures without pneumorectum. METHODS: Functional devices were designed in the Polytechnic School of Engineering of Gijón from 2016 to 2018 using three-dimensional (3D) solid modelling software (Solid-Works®), that allows customization of the device (diameter and length). The devices were made in acrylonitrile butadiene styrene (ABS) by additive manufacturing using an HP Designjet 3D Printer, with fused deposition modelling (FDM) technology. Tests were carried out on mixed simulators (with viscera) and cadavers with a prototype in the form of an open cylindrical base ellipsoid spindle with two bars. In this paper, we present the information of the first series of patients in which this device has been used to perform a full-thikness endoscopic resection of the rectal wall without pneumorectum. The characteristics of the patients, size, and location of the lesion, the type of anesthesia used, the duration of the procedure, hospital stay, complications, and pathology were analyzed. An endoscopic follow-up was also carried out for at least 2 years. RESULTS: Seven interventions were carried out in six patients. The lesions were located at a mean distance of 5 cm from the anal verge and an average area of 11.8 cm2. Four of the procedures were performed with general anesthesia and 3 with spinal anesthesia. Histopathology examination identified 3 adenomas, 3 pT1 and 1 pT2 adenocarcinomas. All excisions were full thickness. En bloc excision was possible in all cases. In only one case of a benign polyp there was a positive lateral margin. As regards complications, there was one case of postoperative rectal bleeding without the need for transfusions. There were no readmissions and no postoperative mortality. CONCLUSIONS: An innovative device made with a 3D printer can be used successfully in transanal endoscopic resections of the rectal wall, with spinal anaesthesia and avoiding the need for pneumorectum.

Differential regulation of rat peripheral 5-HT(2A) and 5-HT(2B) receptor systems: influence of drug treatment.

Most studies of 5-HT(2) receptor regulation have been carried out on the central nervous system (CNS) (which expresses 5-HT(2A) and 5-HT(2C) receptors); very few in vitro studies have addressed the peripheral receptors 5-HT(2A) and 5-HT(2B). The aim of this investigation was to compare the possible short- and long-term processes regulating these peripheral receptors in the rat. The in vitro contractile response elicited by serotonin (5-HT, 10 micro M) in the rat gastric fundus (5-HT(2B) receptor system) was rapid and followed by a partial fade to a steady state, in contrast with the rat thoracic aorta response (5-HT(2A) receptor system), which was more stable, slower and sustained. To characterize drug-receptor interactions, cumulative concentration/response curves (CCRCs) for 5-HT were constructed ex vivo for rat tissues treated with drugs acting at these receptors. Rats were examined 4 or 24 h after a single, i.p. administration of (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)DOI, 1 or 2.5 mg/kg], clozapine, cyproheptadine or rauwolscine (10 mg/kg), 48 h after a single i.p. administration of (+/-)DOI (2.5 mg/kg), clozapine or cyproheptadine (10 mg/kg) or 24 h after the last of with 15 daily i.p. administrations of (+/-)DOI (1 or 2.5 mg/kg), clozapine, cyproheptadine or rauwolscine (10 mg/kg). In the aorta, E(max) (the maximum response elicited by 5-HT) was unchanged 4 h after a single dose of any of the drugs tested. However, 24 h after a single dose, E(max) was lower in animals treated with (+/-)DOI (2.5 mg/kg), clozapine or cyproheptadine than in controls, whilst 48 h after a single dose of (+/-)DOI (2.5 mg/kg), clozapine or cyproheptadine there was no difference in E(max) between experimental and control animals. After chronic treatment with (+/-)DOI (2.5 mg/kg), clozapine and cyproheptadine, E(max) was lower than in controls. In the gastric fundus, E(max) 4 h after a single dose of each drug was lower than in controls, and the response recovered by 24 or 48 h. Following chronic treatment, E(max) was significantly lower than in controls for each drug used. These findings suggest first, that regulation of peripheral 5-HT(2) receptors (5-HT(2A) and 5-HT(2B)) is a functionally significant phenomenon in vivo, and occurs after administration of both agonists and antagonists. Second, the kinetics of peripheral 5-HT(2) receptor regulation were similar in both in vivo and ex vivo experiments. The 5-HT(2B) receptors in rat gastric fundus are more sensitive to drug-induced regulation than the 5-HT(2A) rat aortic receptors. Finally, long-term regulation of both receptors stabilizes short-term desensitization for longer.

New arylpiperazine derivatives with high affinity for alpha1A, D2 and 5-HT2A receptors.

A series of novel long-chain arylpiperazines bearing a coumarin fragment was synthesized and the compounds were evaluated for their affinity at alpha(1), D(2 )and 5-HT(2A) receptors. Most of the new compounds showed high affinity for the three types of receptors alpha(1A), D(2) and 5-HT(2A) which depends, fundamentally, on the substitution of the N(4) of the piperazine ring. From the series emerged compound 6, which had an haloperidol-like profile at D(2) and 5HT(2A) receptors (pK(i) values of 7.93 and 6.76 respectively). The higher alpha(1A) receptor affinity (pA(2)=9.07) of this compound could contribute to a more atypical antipsychotic profile than the haloperidol.

Multiple conformations of native and recombinant human 5-hydroxytryptamine(2a) receptors are labeled by agonists and discriminated by antagonists.

We have expanded previous studies with the 5-hydroxytryptamine (5-HT)(2) receptor agonist (+/-)-1-(2,5-dimethoxy-4-[(125)I]iodophenyl)-2-aminopropane [(+/-)-[(125)I]DOI] in human brain that had shown biphasic competition curves for several 5-HT(2A) receptor antagonists by using new selective antagonists of 5-HT(2A) (MDL100,907) and 5-HT(2C) (SB242084) receptors together with ketanserin and mesulergine. Autoradiographic competition experiments were performed with these antagonists in human brain regions where (+/-)-[(125)I]DOI labels almost exclusively 5-HT(2A) receptors (frontal cortex and striosomes). Furthermore, the effect of uncoupling receptor/G protein complexes on antagonist competition was studied with guanosine-5'-(beta,gamma-imido)triphosphate [Gpp(NH)p]. Competition experiments with (+/-)-[(3)H]1-(4-bromo-2,5-dimethoxyphenil)-2-aminopropane [(+/-)-[(3)H]DOB] were also performed in membranes from Chinese hamster ovary cells (CHOFA4) expressing cloned human 5-HT(2A) receptors. In both systems, ketanserin and MDL100,907 displayed biphasic competition profiles, whereas SB242084 and mesulergine competed monophasically. In absence of antagonist, 100 microM Gpp(NH)p decreased brain (+/-)-[(125)I]DOI specific binding by 40 to 50% and (+/-)-[(3)H]DOB specific binding to CHOFA4 cells by 30%. The remaining agonist-labeled uncoupled sites were still displaced biphasically by ketanserin and MDL100,907, with unaltered affinities. Saturation experiments were performed in CHOFA4 cells. (+/-)-[(3)H]DOB labeled two sites (K(d(h))= 0.8 nM, K(d(l)) = 31.22 nM). Addition of 100 microM Gpp(NH)p resulted in a single low-affinity (K(d) = 24.44 nM) site with unchanged B(max). [(3)H]5-HT showed no specific binding to 5-HT(2A) receptors. These results conform with the extended ternary complex model of receptor action that postulates the existence of partly activated receptor conformation(s) (R*) in equilibrium with the ground (R) and the activated G protein-coupled (R*G) conformations. Thus, both in human brain and CHOFA4 cells, the agonists possibly label all three conformations and ketanserin and MDL100,907 recognize with different affinities at least two of these conformations.

Conformationally constrained butyrophenones with affinity for dopamine (D(1), D(2), D(4)) and serotonin (5-HT(2A), 5-HT(2B), 5-HT(2C)) receptors: synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics.

A series of novel conformationally restricted butyrophenones (6-aminomethyl-4,5,6,7-tetrahydrobenzo[b]furan-4-ones bearing 4-(6-fluorobenzisoxazolyl)piperidine, 4-(p-fluorobenzoyl)piperidine, 4-(o-methoxyphenyl)piperazine, 4-(2-pyridyl)piperazine, 4-(2-pyrimidinyl)piperazine, or linear butyro(or valero)phenone fragments) were prepared and evaluated as antipsychotic agents by in vitro assays for affinity for dopamine receptors (D(1), D(2), D(4)) and serotonin receptors (5-HT(2A), 5-HT(2B), 5-HT(2C)), by neurochemical studies, and by in vivo assays for antipsychotic potential and the risk of inducing extrapyramidal side effects. Potency and selectivity depended mainly on the amine fragment connected to the cyclohexanone structure. Compounds 20b, with a benzoylpiperidine moiety, and 20c, with a benzisoxazolyl fragment, were selective for 5-HT(2A) receptors. The in vitro and in vivo pharmacological profiles of N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(p-fluorobenzoyl)piperidine (20b, QF1003B) and N-[(4-oxo-4,5,6, 7-tetrahydrobenzo[b]furan-6-yl)methyl]-4-(6-fluorobenzisoxazol-3-yl)p iperidine (20c, QF1004B) suggest that they may be effective as antipsychotic (neuroleptic) drugs.

Estudio de la memoria en pacientes esquizofrénicos / A study on memory in schizophrenic patients

Se plantea que en el trabajo práctico diario, al estudiar la memoria de los pacientes esquizofrénicos desde el comienzo de su enfermedad, se ha encontrado que estos enfermos presentan alteraciones significativas en cuanto al volumen como quiera que algunos autores plantean la presencia de alteraciones orgánicas en pacientes con esquizofrenia, en el presente trabajo se realiza un estudio descriptivo de las alteraciones encontradas en la memoria de un grupo de 30 pacientes de la sala "Concha García" del Hospital Psiquiátrico de La Habana, diagnosticadas como esquizofrénicas, de conformidad con el Glosario Cubano de la Clasificación Internacional de Enfermedades Psiquiátricas. Se analizan los resultados obtenidos de los de otras investigaciones realizadas a pacientes con lesiones cerebrales(AU)