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Biomedical subjects

S Rivas

Publications and source records attributed to S Rivas.

At least 19 recordsLinked to original sources
PubMed2004

[Aggressive conservative treatment remains the best option for oesophageal perforation in children].

UNLABELLED: Oesophageal perforation (OP) requires prompt and vigorous treatment. In contrast with adult patients in whom surgical closure of perforation is preferred, non-operative treatment has been the usual approach in children. The present report aims at assessing whether this strategy stands the passage of time. We studied retrospectively the charts of patients treated at our institution for OP between 1991 and 2001. Between these years, we treated 19 episodes of OP in 17 patients aged 5.3 +/- 0,94 years. In 9 cases (4 lye burns, 3 oesophageal atresias, 1 bullous epidermolysis and 1 mucocutaneous candidiasis) OP occurred during dilatation of strictures. Foreign body extraction was the cause in 3 cases, and blunt trauma and sclerosis of varices were the causes in 2 cases each. The last child had multiple gastrointestinal perforation during treatment for leukaemia. Subcutaneous emphysema was seen in 7 instances, pneumomediastinum/pneumothorax in 14, pleural effusion in 9, dyspnoea in 9, severe thoracic pain in 1 and pericardial effusion in 1. The diagnosis was intraoperative in only 2 children but the symptoms and imaging signs prompted vigorous treatment within the first 24 hours in 15 instances. One or more pleural tubes were inserted in 11 cases and pericardial drainage was required once. Perforations closed without direct surgery in 18/19 episodes (16/17 children). Five gastrotomies and 2 jejunostomies were performed and several major abdominal operations were necessary to repair concurrent lesions in a child who sustained severe blunt abdominal trauma and in the one with leukaemic perforations. All these patients survive and all recovered oesophageal function although 2 with intractable lye structures ultimately required oesophageal replacement 6 and 10 months after OP. The only patient in whom direct approach for esophageal necrosis after variceal endosclerosis was unavoidable lost her organ and had a replacement after a successful porto-systemic shunt. CONCLUSIONS: Prompt and aggressive non-operative approach of oesophageal perforations in children allows survival and conservation of the organ and its function in most cases and should remain the first therapeutic choice at this age.

Adolescent↗
PubMed2003

Aggressive conservative treatment of esophageal perforations in children.

BACKGROUND/PURPOSE: In contrast with adult patients in whom surgical closure of the defect is preferred, nonoperative treatment has been the usual approach for esophageal perforation (EP) in children. This report aims to assess whether this strategy stands the passage of time. METHODS: We reviewed retrospectively the charts of 17 patients aged 5.3 +/- 0.9 years (mean +/- SD) treated at our institution for EP between 1991 and 2001. RESULTS: Nineteen episodes of EP were caused by stricture dilation in 9 cases, foreign body extraction in 3, and blunt trauma and sclerosis of varices in 2 cases each. The remaining child had multiple gastrointestinal perforations in the course of chemotherapy for leukemia. Vigorous treatment, consisting of nasopharyngeal aspiration, wide spectrum antibiotics, prompt drainage of effusions and either parenteral or infraesophageal nutritition, was implemented immediately after diagnosis. Perforations were closed without direct surgery in 18 of 19 episodes (16 of 17 children). One or more pleural drains were inserted in 12 cases, and pericardial drainage was required once. Seven gastrostomies, 2 jejunostomies, and one esophagostomy were performed. Several major abdominal operations were necessary to repair concomitant lesions in a child who sustained severe blunt abdominal trauma and in the patient with leukemic perforations. All patients survived, and all recovered esophageal function. However, 2 with intractable lye strictures ultimately required esophageal replacement. The only patient in whom a direct approach for esophageal necrosis due to variceal endosclerosis was unavoidable, lost her organ and had a retrosternal colonic interposition after a successful portosystemic shunt. Excluding patients with other concomitant lesions and the patient who underwent surgery, median length of stay was 11 days (range, 6 to 47). CONCLUSIONS: Prompt and aggressive nonoperative treatment of esophageal perforations in children allows survival with conservation of the organ in most cases and remains, in the authors' hands, the first therapeutic choice at this age.

Abdominal Injuries↗
PubMed2003

[Extensive aganglionosis. Treatment and long term results].

INTRODUCTION: Extensive aganglionosis (EA) that affects the total colon (including or not part of the small intestine), shows more diagnostic problems and it is associated to higher morbidity and mortality rates than the classic cases of Hirschsprung disease (ED). This study takes into account last years cases and their results in the medium and long term. MATERIAL AND METHODS: Between 1983 and 2000, 232 patients suffering ED have been treated. 15 out of those 232 patients showed EA. We took into consideration the diagnosis, surgical procedures, enterocolitis before and after the treatment, the surgical technique and the complications. We analyze the nutritional state and the long term result according to clinical bowel function scoring system continency Scale, considering the surgical possibilities depending on each case. RESULTS: Two patients died due to septics complications, one of them during the neonatal period and the other one at the age of 3. Two other cases became possible candidates to an intestinal transplantation due to the extension of their disease. Five out of the 11 left patients had more than 30 cm of small intestine involved, and another five had involved less than 30 cm from ileocecal valve. The last case showed a total colonic aganglionosis with associated intestinal neuronal displasia. One case was associated with S. Ondine and another one with a 21 triosomia. Two of the patients were brothers and another patient has got a brother suffering from rectosigmoid HD. The surgical techniques used with 13 were: 8 cases using Lester Martin modification (one of them needed redo procedure because of anastomosis leak and perineal fistula), 4 Swenson procedure and one patient was treated by Ziegler's miectomy with prolongated miotomy. Nine of the patients mentioned before, lead a quite life (five L, Martin, 4 Swenson); 2 patients suffering frequent fecal retention crisis. 5 out of the 11 reviewed cases, show a weight and height p > or = 50, 2 below p50, 2 below p25, and 2 under p3. CONCLUSION: EA represents a small percentage of Hirschsprung disease. Although Martin modification is the most widely employed technique in cases of distal ileal involvement, Swenson procedure has provided good results in the long term follow-up with few complications. Intestinal transplantation may be the only choice for long term survival in patients with near total intestinal aganglionosis. Continence improves in the follow-up but few times is normal. Nutritional state should be-controlled by a specialized team.

Child, Preschool↗
PubMed2003

[Giant congenital nevus: past, present and future].

INTRODUCTION: The suitable cutaneous covering for big defects secondary to the removal of giant pigmented lesions has not been obtained yet. Nevus that affect a corporal surface bigger than 75%, have no curative treatment and in the cases of smaller nevus therapeutical possibilities are complex, take too much time and provide unfavourable aesthetic results. MATERIAL AND METHODS: Nineteen patients suffering giant congenital nevus (GCN) have been treated in the last eight years. The GCN affected back (8), scalp (3), face and neck (3), extremities (2), thorax and abdomen (2) and buttocks (1). RESULTS: There has been no melanoma case and all the cases showed a congenital melanocitic nevus as histological result, with plexiforme underlying plexiform neurofibroma in two of them. The treatment was: removal using expansors (6), removal and skin graft (5), multiple sequential removals (7), and removals using a covering of cultured keratinocites (1). CONCLUSION: To sum up, it is essential to choose the technique depending on the individual, taking into account the location, measurement, age and social conditions. In addition to that, the treatment shouldd be the earliest, the most effective, the fastest and the most secure. Moreover, it is very important to know every surgical technique well.

Adolescent↗
PubMed2003

[Early esophageal replacement in patients with esophageal atresia].

INTRODUCTION: When primary anastomosis is not feasible in esophageal atresia esophageal replacement is one of the possible options. We report our experience with this approach in patients with long-gap esophageal atresia. MATERIALS AND METHODS: From 1991 to 2002 we treated 50 children with esophageal atresia. Nine required esophageal replacement because of long-gaps. Six were boys and three girls. Six had isolated atresia, and three had regular atresia with TEF. Associated malformations in 8 patients were: cardiovascular (2), anorectal (2), urogenital (5), intestinal duplication (1), and costovertebral (1). The weight at birth ranged from 1.2 to 3.95 kg (median 2.3). Patients with type I atresia had immediate gastrostomy accompanied by esophagostomy in one. Esophageal anastomosis was impossible or failed in 3 patients with type III EA, who had fistula ligation and esophagostomy. Esophageal replacement was performed at a median age of 4.95 months (range 2.3 to 18), with a median weight of 5.33 (range 2.89 to 11.5 kg.). We used gastric pull-up in 2 cases and colonic transposition in 7 with isoperistaltic left transverse colon in retromediastinal-transhiatal (6) or restrosternal (1) position. Two patients had extramucosal piloromyotomy and 4 had piloroplasty. RESULTS: All patients survive and have functional grafts. Postoperative complications were: pneumonia (1), wound dehiscence with evisceration (2) and salivary fístula (2) which closed spontaneously. In the long range, one patient was operated three times for hernia through the enlarged hiatus, one had one episode of intestinal subobstruction successfully managed with nasogastric aspiration and another one had dumping syndrome for several months. After a median follow-up of 3.15 years (range 1.6 to 6.9) all patients eat normal diets per os. CONCLUSIONS: Esophageal replacement for the treatment of infants with long-gap EA has been in our hands as good as any other option with 100% survival and good functional results. The operation can be safely performed in the first months provided that associated malformations are under control. However, like other options, this approach is not devoid of complications.

Esophageal Atresia↗
PubMed2003

[Severe complications in the treatment of vascular anomalies].

BACKGROUND: Success in the treatment of vascular anomalies during infancy depends on an accurate early diagnosis and a correct therapeutic management. Current available resources can be divided into pharmacologic, endovascular, surgical, and laser. Results are variable, and complications should always be kept in mind. METHODS: We reviewed all patients with vascular anomalies who suffered from major complications directly due to the treatment during the past five years. RESULTS: 1. A patient with an upper lip hemangioma following treatment with interferon after no response to steroids. A long-term severe neutropoenia forced to an early surgical excision of the lesion. 2. A patient suffering from an orbitary hemangioma with severe exoftalmus was treated with interferon because of a steroid-resistance. A spastic diplegia due to interferon reverted after treatment was discontinued. 3. In a patient with a Blue-Rubber Bleb Nevus syndrome, extended percutaneous sclerosis was performed. She developed skin necrosis of the left leg and a permanent sciatic nerve paralysis. 4. In a patient with an arteriovenous malformation on the right leg and gluteous, a femoral artery endoprosthesis was placed because of a massive bleeding. She underwent a total excision of the malformation and developed a recurrent ischemia related to a femoral thrombosis. Finally a foot amputation was needed. 5. A patient with a Kaposi-like hemangio-endothelioma who was following a high-dose prolonged steroid therapy died because of a meningoencephalitis related to a severe immunosuppression. CONCLUSIONS: Treatment of vascular anomalies during childhood need an early accurate diagnosis. If a right therapeutic sequence is not performed, useful drugs can turn into inefficient or dangerous. Most treatment complications in these patients can be avoided.

Blood Vessels↗
PubMed2002

[High flow vascular malformations in children].

Unlike hemangiomas and low-flow vascular malformations which are very common in children, arterial anomalies have small incidence. Differential diagnosis is difficult, and needs a physician familiarized with vascular anomalies. Appropriate treatment must be planned by multidisciplinary team considering the patient's age, and anatomical location. Twenty-eight children with high flow vascular malformations have been treated since 1990 at La Paz Children's Hospital Vascular Anomalies Program. We excluded of the study group patients with central nervous system lesions. 85% of the patients had malformation in stage I or II (according the ISSVA accepted Schöbinger stating) and most of them were erroneously diagnosed as hemangioms with a variety of inappropriate treatments previously performed. Doppler Ultrasound and Magnetic Resonance confirmed malformation flow and extension. Angiography and selective embolization was only considered as therapeutic approach in candidates to surgical resection. 16 patients underwent complete resection of the malformation including one foot and two fingers amputation and five more incomplete resection of the ulcerate area. In conclusion, we did not find age at onset, sex and symptoms relationship. Laser, radiotherapy, surgical ligation or partial resection must be considered inappropriate therapies which may stimulate AVM exacerbation. Only radical surgical procedure after selective endovascular embolization will be successful but then reconstructive surgery should be performed to achieve good aesthetic and functional results.

Adolescent↗
PubMed2002

[Integra Artificial dermis in pediatric reconstructive surgery].

UNLABELLED: The recent release of artificial dermis for general use, has open wide a new field in pediatric reconstructive surgery. The aim of this paper is to analyze the results of Integra artificial dermis in our Plastic Surgery Department. MATERIALS AND METHODS: The records of the patients treated with Integra between february 1999 and january 2001 were analyzed, focusing on the indications, the complications and the final results. RESULTS: Fourteen Integra implantation procedures in 11 patients aged 16 months to 12 years (mean +/- SD: 80.9 +/- 48.5 months) were performed. Indications were: acute burns in 5 cases, burns sequelae in 5, and partial extirpation of a congenital giant nevus in the last one. Integra was used to replace between 2 and 30% of total body surface area. The percentage of "take" of skin grafts was 85%. The most frequent early complication was the development of infection under the Integra; it occurred in 2 cases and artificial dermis had to be partially removed. Hypertrophic scars developed in 2 patients; both had refused pressure garments. Cosmetic results in the remaining 9 patients are considered excellent. CONCLUSIONS: The use of artificial dermis has settled as a new procedure in plastic pediatric surgery. In spite of possible complications, the easy manipulation and the good results make Integra a perfect skin substitute in several cutaneous disorders.

Biocompatible Materials↗
PubMed2002

[Decrease in bacterial translocation in burned children treated with controlled nutritional support].

INTRODUCTION: Alteration in epithelial enteric cells are the main cause of bacteria translocation and local and systemic infections. Our aim is to evaluate these infections in burned children treated with enteral nutrition and compare the results with our previous observations. Material and methods. We designed a prospective study including 50 patients (0-14 years) with TBSA > 10% (total body surface area). Bacteriological cultures were performed at their admittance and weekly until the discharge. Nutritional necessities were evaluated using calorimetry. Nutritional support was supplied by nasoduodenal tube at continuous rates. RESULTS: Three (6%) patients with enteral nutrition (Group 1) showed positive blood cultures (two of them by enteric bacteriae). 14 patients (28%) showed local infections (five by enterococci). We performed a retrospective study in a homogenous group of 44 patients (Group 2), previously treated in our Department without controlling nutrition. We found five (11.3%) positive blood cultures (four by enteric bacteriae) and 22 (50%) local infections (eleven by enteric bacteriae). The improvement of systemic and local infection rates and the decrease in infections caused by enteric bacteriae were statistically significative (p < 0.05). CONCLUSIONS: A controlled nutritional support is a main cause of the improvement in infection rates and decrease in bacterial translocation in pediatric burned patients.

Adolescent↗
PubMed2001

No evidence for binding between resistance gene product Cf-9 of tomato and avirulence gene product AVR9 of Cladosporium fulvum.

The gene-for-gene model postulates that for every gene determining resistance in the host plant, there is a corresponding gene conditioning avirulence in the pathogen. On the basis of this relationship, products of resistance (R) genes and matching avirulence (Avr) genes are predicted to interact. Here, we report on binding studies between the R gene product Cf-9 of tomato and the Avr gene product AVR9 of the pathogenic fungus Cladosporium fulvum. Because a high-affinity binding site (HABS) for AVR9 is present in tomato lines, with or without the Cf-9 resistance gene, as well as in other solanaceous plants, the Cf-9 protein was produced in COS and insect cells in order to perform binding studies in the absence of the HABS. Binding studies with radio-labeled AVR9 were performed with Cf-9-producing COS and insect cells and with membrane preparations of such cells. Furthermore, the Cf-9 gene was introduced in tobacco, which is known to be able to produce a functional Cf-9 protein. Binding of AVR9 to Cf-9 protein produced in tobacco was studied employing surface plasmon resonance and surface-enhanced laser desorption and ionization. Specific binding between Cf-9 and AVR9 was not detected with any of the procedures. The implications of this observation are discussed.

Animals↗
PubMed2000

Synovectomy with rifampicine in haemophilic haemarthrosis.

The purpose of this paper was to assess the effectiveness of intra-articular injected rifampicine in haemophilic patients in order to achieve synovectomy by preventing repeated intra-articular bleeding. We have used this technique in haemophilic patients previously and reported our results on 13 cases [1]. Two hundred and fifty milligrams of rifampicine was injected into the elbow and ankle joints and 500 mg was injected into knee joints with 3-10 mL of lidocaine, depending on the joint size. The injections were repeated once a week for 7 weeks. Patients were only covered with antihaemophilic factor on the day of the injection at 30% above their coagulation level. We evaluated the results using two measures: subjective reports from the patient and objective assessment by the examiner. In the subjective reports the patient graded the results from their own perspective from 1 (poor) to 10 (excellent): 1-3, poor; 4-6, fair; 7-8, good; and 9-10, excellent. In the objective reports the grading was: excellent ('dry joint', full function, no haemarthrosis, no synovitis); good (clinical improvement, synovitis, reduction of haemarthroses, full function); fair synovitis (reduction of haemarthroses, no change in function); poor synovitis (persistent haemarthroses). This paper reports on the results of 38 patients with 39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees, nine elbows and eight ankles. Subjectively, there were excellent results in 21 joints (11 knees, six elbows and four ankles) good results in 15 joints (eight knees, three elbows and four ankles), fair results in two knees and a poor result in one knee. Objectively, results obtained were excellent in 20 joints (11 knees, six elbows and three ankles); good in 17 (nine knees, three elbows and five ankles); fair in one knee and poor in one knee.

Adolescent↗
PubMed2000

Functional, c-myc-tagged Cf-9 resistance gene products are plasma-membrane localized and glycosylated.

The Cf-9 resistance gene from tomato confers resistance to races of the fungal pathogen Cladosporium fulvum that express the corresponding avirulence gene, Avr9. Avr9 encodes a secreted peptide. To investigate Cf-9 function, we tagged the Cf-9 protein with a triple myc epitope at either the amino- or carboxy-terminus of the mature protein. Tobacco plants carrying these constructs activate a defence response to Avr9 peptide. The Cf-9 sequence predicts a protein of 94 kDa, with 22 glycosylation sites. Using c-myc antibodies, c-myc : Cf-9 protein was detected as a unique band with a molecular size of 160 kDa. The band shifted to approximately 105 kDa after glucosidase treatment, indicating that Cf-9 protein is highly glycosylated. Plasma membranes were isolated using two-phase partitioning, and c-myc : Cf-9 was enriched in these fractions, indicating that Cf-9 is a plasma membrane protein. This was confirmed by silver-enhanced immunogold labelling of tobacco protoplasts carrying the amino-terminal c-myc tag; a higher labelling density was observed on the surface of protoplasts derived from c-myc : Cf-9 tobacco compared to untransformed control. The presence of Cf-9 in the plasma membrane is consistent with its role in conferring recognition of the extracellular Avr9 peptide.

Alleles↗
PubMed1998

Congenital deficiency of the tibia: a report on 22 cases.

Congenital deficiency of the tibia (tibial hemimelia, aplasia, or dysplasia) is very rare, with an incidence of approximately 1 per 1 million live births. The disorder usually is accompanied by other congenital anomalies on the same limb or other parts of the body. A report is made of 22 limbs observed in 18 patients from 1970 to 1987 at San Juan de Dios Hospital in Caracas, Venezuela, with more than a 5-year follow-up. The report includes 11 girls and 7 boys, with observations of 11 left and 11 right tibiae. Familial antecedents were present in four patients: brother and sister and two brothers. According to the classification by Jones, Barnes, and Lloyd-Roberts, there were nine cases of type Ia, four of type Ib, three of type II, two of type III, and four of type IV. The foot of the affected limb was normal in only 12 cases. Treatment, always surgical, consisted of T/K amputation in 10 cases of types Ia and Ib, fibula pro tibia and B/K amputation in 1 case of type II, Syme amputations in 2 cases of type III, and astragalectomy and closure of diastasis in 4 cases of type IV deformity. Patients in five cases refused treatment. The sooner the amputation is performed, the easier and faster the rehabilitation and adaptation to the prosthesis. An early amputation is accepted by the child as a "congenital amputation."

Abnormalities, Multiple↗
PubMed1997

TrwD, a protein encoded by the IncW plasmid R388, displays an ATP hydrolase activity essential for bacterial conjugation.

A 1.7-kilobase pair segment from the conjugative transfer region of plasmid R388 DNA was cloned and sequenced. It contained trwD, a gene essential for plasmid R388 conjugation, for expression of the conjugative W-pilus and for sensitivity to phage PRD1. The deduced amino acid sequence of TrwD showed homology to the PulE/VirB11 superfamily of potential ATPases involved in various types of transport processes. A fusion of trwD with the glutathione S-transferase (GST) was constructed, and the resulting fusion protein was purified from overproducing bacteria. Factor Xa hydrolysis of GST-TrwD and further purification rendered TrwD protein with more than 95% purity. Antibodies raised against TrwD localized it both in the soluble fraction and in the outer membrane of Escherichia coli. TrwD is probably a peripheral outer membrane protein because it could be solubilized by increasing salt concentration to 0.5 M NaCl in the lysis buffer. Both purified GST-TrwD and TrwD could hydrolize ATP. ATPase activity increased 2-fold in the presence of detergent-phospholipid mixed micelles. To study the importance of the nucleotide-binding site, Walker box A (GXXGXGK(T/S)), present in TrwD, the conserved lysine residue was replaced by glutamine. The mutant protein, expressed and purified under the same conditions as the wild type, did not exhibit ATPase activity. TrwD(K203Q) was not able to complement the mutation in trwD of the R388 mutant plasmid, suggesting the essentiality of the ATPase activity of the protein in the conjugative process. Furthermore, the dominant character of this mutation suggested that GST-TrwD(K432Q) was still able to interact either with itself or with other component(s) of the conjugative machinery.

Adenosine Triphosphatases↗
PubMed1996

Radioactive synoviorthesis in hemophilic hemarthrosis: materials, techniques, and dangers.

Radioactive synoviorthesis with 198Au, 90Y, 186Re, and 31P would seem to be the treatment of choice for recurrent hemarthroses in hemophilia. The clinical results, obtained by different centers, show a definite diminution of hemarthroses in 88% of cases. The advantages of radioactive synoviorthesis compared with surgical synovectomy are: better results, the requirement of substantially reduced antihemophilic factor, the possibility of performing the procedure on multiple cases concurrently on an ambulatory basis, no interference with articular range of movement, and the low cost of the procedure. In cases of failure, the procedure can be repeated after 6 months, and on as many as 3 occasions. Studies performed on the chromosomal changes that could be attributed to the radioactive material show the disappearance of these alterations a few years after treatment. No physical changes have been found that could be attributed to cytogenic alteration (hematologic or other) in any reported patients.

Adolescent↗
PubMed1994

An intrinsic-tryptophan-fluorescence study of phage phi 29 connector/nucleic acid interactions.

The protein p10 of bacteriophage phi 29 assembled into connectors exhibit an intrinsic fluorescence with an emission peak centered at 335 nm, which suggests a hydrophobic environment of the three tryptohan residues that the protein contains. Upon incubation with linear DNA (but not with circular DNA), a decrease in the connector intrinsic fluorescence is measured which does not show any sequence specificity. The decrease in fluorescence is not observed when DNA is incubated with proteolyzed connectors, which lack the DNA-binding domain, suggesting that the fluorescence quenching is related to the binding of DNA to the phi 29 connectors. Acrylamide quenching studies reveal a higher accessibility of tryptophan residues to the quencher when the connector is bound to DNA. Protein denaturation by guanidine hydrochloride occurs at lower denaturant concentrations in the presence of linear DNA (but not circular DNA) than in its absence, suggesting a conformational change of phi 29 connector upon binding to linear DNA. This hypothesis is supported by the fact that the proteolyzed connectors, which do not bind DNA, are denatured at the same denaturant concentration, regardless of the presence of DNA. phi 29 connectors also bind RNA, but this interaction does not exert any effect on acrylamide quenching or guanidine hydrochloride denaturation. This result, together with that showing that proteolyzed connectors are able to interact with RNA, reinforces the idea that phi 29 connectors have two independent domains for interaction with DNA and RNA.

Bacillus Phages↗
PubMed1994

Reversal of extinction by scopolamine.

The aim of this experiment was to determine the effects of muscarinic blockade on extinction of passive avoidance conditioning. Rats were trained with a foot shock of 2.5, 3.0, or 6.0 mA and were tested for retention for 8 weeks (once weekly). Five minutes before the seventh test they were injected with 8 mg/kg scopolamine. The groups that had been trained with 2.5 and 3.0 mA showed extinction, which was reversed by the scopolamine; the overreinforced group (6.0 mA) did not show extinction and the scopolamine did not alter the conditioned response. The data support the hypothesis that extinction represents the learning of a new response sustained by a set of cholinergic neurons, different from that which mediated original passive avoidance learning.

Acetylcholine↗