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Biomedical subjects

A Sandor

Publications and source records attributed to A Sandor.

At least 19 recordsLinked to original sources
PubMed2002

Opposite regulation of uncoupling protein 1 and uncoupling protein 3 in vivo in brown adipose tissue of cold-exposed rats.

Earlier we reported a 14-fold increase of glycogen in the brown adipose tissue (BAT) in rats when the animals were placed back from cold to neutral temperature. To elucidate the mechanism, here we compared the level of glucose transporter 4 (GLUT4) protein, uncoupling protein (UCP) 1 and UCP3 mRNA and protein expressions in the BAT under the same conditions. We found that the increased GLUT4 level in cold was maintained during the reacclimation. After 1 week cold exposure the mRNA and protein content of UCP1 increased parallel, while the protein level of UCP3 decreased, contrary to its own mRNA level.

Acclimatization↗
PubMed2000

Metabolism of carnitine in phenylacetic acid-treated rats and in patients with phenylketonuria.

The effect of metabolites accumulating in phenylketonuria (PKU) was investigated on carnitine metabolism in rats and in patients with PKU. Of phenylacetic acid (PEAA), phenylpyruvic acid and homogentisic acid the PEAA was found to be the most effective in inhibiting carnitine biosynthesis in rats. Following 60 min, a single intraperitoneal dose of PEAA the relative conversion rate, i. e. the hydroxylation, of tracer [Me-(3)H]butyrobetaine to [Me-(3)H]carnitine decreased from 62.2+/-6.00% to 39.4+/-5.11% (means+/-S.E.M., P<0.01) in the liver, in the only organ doing this conversion in rats. The conversion of loading amount of unlabeled butyrobetaine to carnitine was also markedly reduced. The impaired hydroxylation of butyrobetaine was reflected by a reduced free and total carnitine levels in the liver and a reduced total carnitine concentration in the plasma. PEAA decreased the hepatic level of glutamic acid and alpha-ketoglutaric acid (alpha-KG), suggesting a mechanism for the reduced flux through the butyrobetaine hydroxylase enzyme, because alpha-KG is an obligatory co-enzyme. In the plasma and urine of PKU patients on unrestricted diet, markedly decreased total carnitine levels were detected. In the liver of PEAA-treated rats and urine of PKU patients, a novel carnitine derivative, phenacetyl-carnitine was verified by HPLC and gas chromatography-mass spectrometry.

Adult↗
PubMed2000

The feasibility and accuracy of diagnostic laparoscopy in the septic ICU patient.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) and sepsis of unknown origin are common complications of critically ill patients in the ICU. These patients frequently have unreliable clinical exams and are candidates for exploratory laparotomy. Although abdominal CT is commonly used because it is less invasive than laparotomy, it is often unreliable or unobtainable. Bedside laparoscopy is an alternative technique that may be more accurate than CT in selected patients and less invasive than laparotomy. METHODS: We performed diagnostic laparoscopy (DL) in a series of ICU patients with SIRS/septic state of unknown origin between May 1997 and June 1998. All patients were unstable and required significant respiratory and hemodynamic support. Laparoscopy was either performed in the ICU at the patient's bedside or in the operating room. CT scan of the abdomen had been performed on most of the patients who were stable enough to transport. Confirmation of diagnosis was obtained either by laparotomy, autopsy, or clinical recovery. RESULTS: Among the 17 eligible patients, 16 underwent successful DL. Insufflation was impossible in one patient because of high intraabdominal pressure. Bedside evaluations were performed in 14 of the 17 patients. There were no complications from the laparoscopy. Six patients were identified as positive (four intestinal ischemia, two cholecystitis); the other 10 had negative explorations. Follow-up on two patients with negative laparoscopy was incomplete due to denied postmortem. Laparoscopic diagnoses were confirmed in the remaining 14 patients by laparotomy (six cases), postmortem (three cases), or recovery (five cases), with an accuracy of 100%. The overall accuracy of abdominal CT obtained in nine of the 14 patients was 33%. CONCLUSIONS: DL in a select group of critical ICU patients is safe and accurate, whereas CT scan tends to be inaccurate and is often unobtainable due to patient instability. Performing the procedure at the bedside can expedite the diagnosis, eliminate the burden for transfer, and save on anesthesia and operating room charges.

Feasibility Studies↗
PubMed2000

Suturing and knotting techniques for thoracoscopic cardiac surgery.

The preceding description of E-CABG may seem excessively detailed, even redundant, for trained cardiac surgeons; however, the authors' extensive experience with training surgeons on endoscopic techniques suggests that, despite a high level of proficiency and dexterity that a surgeon may possess in open surgery, becoming equally proficient and dexterous in the endoscopic environment is not simple. Participating in an in-depth, systematic endoscopic microvascular surgery training program in a laboratory setting is essential before applying the previously described E-CABG techniques in humans. The E-CABG procedure is one of the most challenging endoscopic techniques. Successful completion of this procedure requires that the surgeon be motivated to succeed and willing to invest the time and effort necessary to develop the new skills. Also critical is the avoidance of the temptation to use devices and systems that promise to obviate the need to bother with learning these difficult endoscopic skills. Long term results of the minimally invasive approach remain to be defined. However, some early studies of port-access procedures are encouraging. To date, a prospective randomized clinical trial comparing conventional LAD bypass to E-CABG has not been conducted. Although most investigators believe that long term patency of the IMA to the LAD using either technique should be the same, this is as yet unproven. Nonetheless, the adaption of endoscopic skills by the cardiac surgeon will further advance the evolution of this specialty.

Coronary Artery Bypass↗
PubMed2000

Hand-assisted laparoscopic aortobifemoral bypass grafting.

OBJECTIVE: Aortobifemoral bypass grafting is a durable operation for arterial reconstruction in patients with symptomatic aortoiliac occlusive disease. In several small laparoscopic series technically demanding aortic operations have been described that have not gained widespread acceptance or applicability. To simplify the laparoscopic approach to the aorta, we have developed a technique of aortobifemoral bypass grafting that uses hand-assisted laparoscopic surgery (HALS) to minimize the complexity of aortic dissection and reconstruction. METHODS: Five patients with symptomatic aortoiliac occlusive disease underwent successful HALS aortobifemoral bypass grafting. With the use of a specialized sleeve device (Hand-Port), an operative hand was introduced into the laparoscopic field while pneumoperitoneum was maintained. Laparoscopic dissection of the infrarenal aorta was then performed with retraction provided by the operative hand. Proximal aortic anastomosis was performed with an open technique through the same 7.5-cm Hand-Port incision, and femoral anastomoses were performed in the standard fashion. RESULTS: Five hand-assisted laparoscopic aortobifemoral bypass grafts were performed (two end-to-end, three end-to-side proximal anastomoses). Mean operative time was 231 minutes. Mean blood loss was 440 mL. All patients underwent extubation immediately after surgery, were ambulatory on postoperative day (POD) 1, and were tolerating their diet by POD 3. The mean length of hospital stay was 3.8 days. One patient was discharged on POD 5 and started a clear liquid diet after a self-limiting postoperative ileus. All patients were asymptomatic and back to full activity/work by 14.6 days postoperatively, on average (range, 11-20 days). CONCLUSION: The HALS offers the advantages of tactile feedback, flexible retraction, and the introduction of conventional surgical instruments, all of which extend laparoscopic surgery and its established benefits to a wide array of more complex surgical problems, including major vascular surgery. Ease of performance, shorter hospital stays, and faster recovery times all suggest that HALS may become a valuable adjunct to conventional aortobifemoral bypass grafting.

Adult↗
PubMed2000

Hand-assisted laparoscopic surgery (HALS) with the HandPort system: initial experience with 68 patients.

OBJECTIVE: To evaluate the feasibility and potential benefits of hand-assisted laparoscopic surgery with the HandPort System, a new device. SUMMARY BACKGROUND DATA: In hand-assisted laparoscopic surgery, the surgeon inserts a hand into the abdomen while pneumoperitoneum is maintained. The hand assists laparoscopic instruments and is helpful in complex laparoscopic cases. METHODS: A prospective nonrandomized study was initiated with the participation of 10 laparoscopic surgical centers. Surgeons were free to test the device in any situation where they expected a potential advantage over conventional laparoscopy. RESULTS: Sixty-eight patients were entered in the study. Operations included colorectal procedures (sigmoidectomy, right colectomy, resection rectopexy), splenectomy for splenomegaly, living-related donor nephrectomy, gastric banding for morbid obesity, partial gastrectomy, and various other procedures. Mean incision size for the HandPort was 7.4 cm. Most surgeons (78%) preferred to insert their nondominant hand into the abdomen. Pneumoperitoneum was generally maintained at 14 mmHg, and only one patient required conversion to open surgery as a result of an unmanageable air leak. Hand fatigue during surgery was noted in 20.6%. CONCLUSIONS: The hand-assisted technique appeared to be useful in minimally invasive colorectal surgery, splenectomy for splenomegaly, living-related donor nephrectomy, and procedures considered too complex for a laparoscopic approach. This approach provides excellent means to explore, to retract safely, and to apply immediate hemostasis when needed. Although the data presented here reflect the authors' initial experience, they compare favorably with series of similar procedures performed purely laparoscopically.

Abdomen↗
PubMed1999

A dramatic accumulation of glycogen in the brown adipose tissue of rats following recovery from cold exposure.

In a morphological study of brown adipose tissue (BAT) of rats returned after exposure to cold (+5 degrees C) to neutral temperature (+25 degrees C), striking periodic acid Schiff staining was observed, indicating substantial glycogen accumulation. Enzymatic analysis revealed that the glycogen content increased from the 4.05 +/- 0.51 (micromol glucose unit per gram of tissue, mean +/- SE) control value to 57.3 +/- 9.66 when the animals were returned to neutral temperature for 24 h after a 1-week cold period. Glycogen repletion was also observed in liver and skeletal muscle; however, the glycogen levels in these tissues never exceeded the control values. The accumulation of glycogen in the BAT started by the 3rd hour of replacement and peaked by the 24th hour. This glycogen was readily utilized during the next short cold exposure of the animals. The plasma leptin concentration was reduced at the cold temperature. The hexokinase II activity in the BAT increased to 29.3 +/- 1.46 vs the 11.8 +/- 1.06 control (mU/mg protein +/- SE) after a 1-week cold exposure and this level was maintained during the return to neutral temperature. The total glycogen synthetase (GStot) and the glycogen synthetase a activity also increased after a 1-week cold exposure and increased further during the replacement. The level of GStot reached 26.9 +/- 1.39 vs 9.54 +/- 1.43 control by the 24th hour of replacement. At the same time, the glycogen phosphorylase a activity declined during the replacement. The concentration of glucose 6-phosphate (an activator of GS) decreased in the cold but returned to normal during the replacement. These changes in the BAT are in favor of glycogen synthesis.

Adipose Tissue, Brown↗
PubMed1999

Laparoscopic gastrectomy in the porcine model: our initial experience with a new hand-assist device.

Many advanced laparoscopic cases remain technically difficult and are less widely accepted. To a great extent, advanced laparoscopic surgery is handicapped by the loss of a surgeon's tactile sense. The concept of introducing the surgeon's hand as an aid to minimally invasive surgery has been described. We report a new hand-assist device designed to allow the introduction of the surgeon's hand, wrist, and forearm through a small incision in the abdomen to assist laparoscopic surgery with pneumoperitoneum. Important factors in the hand-assist design are ease of use, reliable maintenance of pneumoperitoneum, and minimal hand/arm fatigue, which were met with this device.

Animals↗
PubMed1998

A retrospective analysis of 1570 appendiceal carcinoids.

OBJECTIVE: Information about the management and outcome of appendiceal carcinoids is sparse, because few series comprise more than 100 cases. In this study we have analyzed the epidemiology of 1570 appendiceal carcinoids, to compare outcome with other gastrointestinal carcinoid tumors. METHODS: We evaluated 1570 appendiceal carcinoids in a series of 8305 carcinoid tumors from the SEER, the End Results Group, and the Third National Cancer Survey programs of the National Cancer Institute over the time period 1950-1991. RESULTS: Appendiceal carcinoids comprised 18.9% of all carcinoid tumors and exhibited a marked female predominance (M/F ratio: 0.47). Age-adjusted incidence rates were 1.7-fold higher in women compared to men. Appendiceal carcinoids present earlier (average age: 42.2 yr) than other gastrointestinal carcinoids (62.9 yr) or noncarcinoid appendiceal tumors (61.9 yr). At the time of diagnosis 35.4% were nonlocalized. The overall 5-yr survival for localized lesions was 94%, for regional invasion 84.6%, and for distant metastases 33.7%. The 5-yr survival of appendiceal carcinoids (85.9%) was the highest among all types of carcinoid tumors. In 14.6% noncarcinoid tumors at other sites were also evident. CONCLUSION: The high relative incidence of carcinoid tumors in the appendix is still poorly understood. The good overall 5-yr survival rates of appendiceal carcinoids as opposed to other carcinoids represents either a different biological behavior, earlier diagnosis, or expeditious management (appendectomy). However, the increased likelihood of coexisting neoplasms and the not uncommon presentation of metastatic disease should warrant careful evaluation and postoperative follow-up of such lesions.

Adult↗
PubMed1997

An analysis of 8305 cases of carcinoid tumors.

BACKGROUND: Carcinoid tumors are unusual and most reports are anecdotal or limited in number. A series of 2837 cases was published in 1975. No recent large series is available. METHODS: The authors evaluated 5468 cases identified by the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NCI) from 1973 to 1991 together with 2837 carcinoid cases previously registered by 2 earlier NCI programs. To the authors' knowledge, the 8305 carcinoid tumors analyzed represent the largest current epidemiology series to date. RESULTS: The most frequent sites for carcinoids were the gastrointestinal (GI) tract (73.7%) and the bronchopulmonary system (25.1%). Within the GI tract, most occurred in the small bowel (28.7%), appendix (18.9%), and rectum (12.6%). For all sites, age-adjusted incidence rates were highest in African American males (2.12 per 100,000 population per year). Associated noncarcinoid tumors were frequent in conjunction with small intestinal (16.6%), appendiceal (14.6%), and colonic carcinoids (13.1%). The highest percentage of nonlocalized lesions were noted for pancreatic (76.1%), colonic (71.2%), and small intestinal carcinoids (70.7%) and this corresponded to their poor 5-year survival rates (34.1%, 41.6%, and 55.4%, respectively). The best 5-year survival rates were recorded for appendiceal (85.9%), bronchopulmonary (76.6%), and rectal carcinoids (72.2%). These exhibited invasive growth or metastatic spread in only 35.4%, 27.2%, and 14.2% of cases, respectively. CONCLUSIONS: Carcinoids appear to have increased in incidence in the past 20 years. In part, this may be due to different surgical rules of the various registries, improved diagnostic technology, and increased awareness. A cumulative analysis of all types of carcinoid tumors in the SEER group indicates that in 45.3% metastases are already evident at the time of diagnosis. The overall 5-year survival rate of all carcinoid tumors regardless of site was 50.4% +/- 6.4%.

Black or African American↗
PubMed1997

The diagnosis and management of adult intussusception.

BACKGROUND: While intussusception is relatively common in children, it is a rare clinical entity in adults, where the condition is almost always secondary to a definable lesion. DATA SOURCES: Thirteen cases of intussusception occurring in individuals older than 16 were encountered at our institute between 1981 and 1994. RESULTS: Presenting signs/symptoms included recurrent bowel obstruction, intermittent pain, and red blood per rectum. Correct preoperative diagnosis was made in six patients using colonoscopy, flexible sigmoidoscopy, upper gastrointestinal (GI) series and computed tomography (CT). At surgery the lead point was identified in the small intestine in eight cases, in the colon in four cases, and one small intestinal intussusception was considered idiopathic. Twelve patients underwent laparotomy and one patient was both diagnosed and treated by colonoscopy alone. CONCLUSIONS: Adult intussusception is an unusual cause of bowel obstruction. The likelihood of neoplasia, particularly in the colon as a cause, is high. Operative management is thus almost always necessary.

Adolescent↗
PubMed1997

Helicobacter pylori lipopolysaccharide stimulates histamine release and DNA synthesis in rat enterochromaffin-like cells.

BACKGROUND & AIMS: Helicobacter pylori alterations in gastric acid output and mucosal proliferation may involve the enterochromaffin-like (ECL) cell. To test whether H. pylori affects ECL cell histamine secretion and proliferation, the effect of lipopolysaccharide (LPS) on ECL cell function in vitro was investigated. METHODS: Using a rat ECL cell preparation of high purity (+/-95%), basal and stimulated histamine secretion and DNA synthesis were measured by enzyme immunoassay and bromodeoxyuridine (BrdU) uptake, respectively. RESULTS: Escherichia coli LPS (10(-12) to 10(-6) mol/L) had no effect on basal and stimulated histamine secretion at concentrations of > 10(-6) mol/L. H. pylori LPS stimulated basal and gastrin-stimulated histamine secretion. These effects were completely inhibited by somatostatin (10(-10) mol/L) but not by the gastrin receptor antagonist L365,260 at 10(-6) mol/L. E. coli LPS had a weak stimulatory effect on ECL cell BrdU uptake at 10(-6) mol/L but had no effect on gastrin-stimulated BrdU uptake. H. pylori LPS did not stimulate basal synthesis but significantly increased (1.5-fold) gastrin-stimulated BrdU uptake. CONCLUSIONS: H. pylori influences both ECL cell proliferation and secretion in vitro. An interaction between H. pylori LPS and ECL cells may contribute to the reported abnormalities in acid secretion and gastric pathobiology noted in H. pylori infections.

Animals↗
PubMed1997

A 40-year analysis of 265 gastric carcinoids.

OBJECTIVES: Gastric carcinoid tumors were previously regarded as rare, benign neoplasms. Few data are available on the epidemiology of this lesion. METHODS: We have analyzed the End Results Group (1950-1969), the Third National Cancer Survey (1969-1971) and the Surveillance, Epidemiology, and End Results (SEER, 1973-1991) databases of the National Cancer Institute. The three files consist of 8305 carcinoid cases collectively, including 265 gastric carcinoids. RESULTS: The percentage of gastric carcinoids among all gastric malignancies has increased from 0.3% to 0.54%. The black:white ratio declined from 0.36 to 0.17 as well as the male:female ratio from 0.9 to 0.57. The age-adjusted incidence rates have increased in white females but are much higher for the black population. Gastric carcinoids are associated with other malignant neoplasms in 7.8% of cases. The 5-yr survival rates for localized lesions, with regional and with distant metastases, were 48.6%, 39.9%, and 10%, respectively. CONCLUSIONS: Gastric carcinoids have increased in incidence over the last 20 yr. This may represent either improved diagnostic techniques, increased awareness, or a real change in incidence. Poor 5-yr survival rates indicate that gastric carcinoid tumors exhibit an aggressive biological behavior.

Age Distribution↗
PubMed1996

Inhibition of carnitine biosynthesis by valproic acid in rats--the biochemical mechanism of inhibition.

The anticonvulsive drug, valproic acid (VPA), inhibits the biosynthesis of carnitine, and may contribute in this way to carnitine deficiency associated with VPA therapy. The conversion of [3H]-butyrobetaine into [3H]-carnitine was determined 60 min following a single intraperitoneal (i.p.) dose of 1.2 mmol/kg VPA in rats. The fraction of radioactivity found in [3H]-carnitine in the liver decreased from 63.2 +/- 1.50% to 39.2 +/- 1.11% (mean +/- SEM). Total carnitine in the liver also decreased, whereas the precursor butyrobetaine increased from 5.01 +/- 0.71 nmol/g to 8.22 +/- 0.82 nmol/g (mean +/- SEM). VPA also exhibited a dramatic effect on the conversion of an unlabeled loading amount of butyrobetaine. The increment in total carnitine caused by butyrobetaine in liver was reduced from 161 +/- 15.4 nmol/g to 53.2 +/- 5.11 nmol/g (mean +/- SEM). These data prove that VPA reduces the flux through butyrobetaine hydroxylase (EC 1.14.11.1.). The drug in vitro, however, did not inhibit the enzyme directly. Searching for the mechanism of action, we found that VPA decreased the level of alpha-ketoglutarate (alpha-KG; a cofactor of butyrobetaine hydroxylase) from 73.5 +/- 2.90 nmol/g to 52.9 +/- 2.2 nmol/g (mean +/- SEM) in the liver. The level of 1-glutamate showed a rather dramatic decrease in the liver. Moreover, alpha-KG proved to have a protective role against VPA in the [3H]-butyrobetaine conversion experiment.

Acetyl Coenzyme A↗
PubMed1996

Why laparoscopic cholecystectomy today?

Traditional open cholecystectomy became the "gold standard" of surgical treatment for symptomatic gallstone disease during the last century. In spite of its good results, clinicians have been trying to establish effective nonsurgical methods of eliminating gallstones. Although oral, percutaneous, or retrograde litholysis can be used effectively for cholesterol stones, these represent only 10% of all gallstones. Moreover, intracorporeal lithotripsy is an invasive method, and while extracorporeal shock wave lithotripsy is a promising procedure, even after careful selection, only 70%-80% of the patients become stone-free within 1 year. In fact, none of the methods which leave the gallbladder intact are free of complications, and they are followed by 50% stone recurrence within 5 years. Since 1987, laparoscopic cholecystectomy has become the procedure of choice as it is safe and only minimally invasive. We believe that the laparoscopic technique is a promising way to the surgery of the future.

Bile Acids and Salts↗
PubMed1996

Somatostatin receptor regulation of gastric enterochromaffin-like cell transformation to gastric carcinoid.

BACKGROUND: Although somatostatin is recognized as an inhibitor of neuroendocrine cell secretion, its effect on cell proliferation has not been well defined. Generation of low acid and hypergastrinemia through irreversible H2-receptor blockade (loxtidine) in the African rodent mastomys results in gastric carcinoids (ECLomas) within 4 months. This study was undertaken to evaluate and characterize the precise somatostatin receptor (SSTR) subtype on the mastomys enterochromaffin-like (ECL) cell and to define its role in the regulation of ECL cell secretion and proliferation. METHODS: A pure preparation (approximately 90%) of ECL cells was derived by a combination of pronase digestion and density gradient separation. We assessed the effect of somatostatin (10(-15) to 10(-7) mol/L) on gastrin-stimulated ECL cell histamine secretion and DNA synthesis (bromodeoxyuridine uptake). SSTR2 subtype was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) using gene specific primers and mRNA isolated from normal and hypergastrinemia-induced ECLoma. The polymerase chain reaction product was confirmed by Southern analysis, subcloned, and sequenced. RESULTS: Somatostatin inhibited both gastrin-stimulated histamine secretion (IC50, 5 x 10(-13) mol/L) and DNA synthesis (IC50, 10(-10) mol/L). SSTR2 was identified in the mastomys' brain, and both normal and tumor ECL cells and comparison of the brain and ECL cell SSTR2 nucleotide sequences revealed homology of 99%. CONCLUSIONS: The SSTR2 is expressed by the mastomys' ECL cell and ECLoma. Receptor activation inhibits both ECL cell secretory and proliferative functions.

Animals↗
PubMed1996

Neurohormonal modulation of rat enterochromaffin-like cell histamine secretion.

BACKGROUND & AIMS: Gastric mucosal cells and nerve terminals contain at least acetylcholine, adrenergic agents, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, serotonin, gamma-amino-butyric acid, neurokinins A and B, neurotensin, neuropeptide Y, peptide YY, gastrin-releasing peptide, somatostatin, and [Met5]enkephalin. Although some of these agents have been implicated as regulators of gastric acid secretion, their site and mechanism of action is not well understood. The aim of this study was to investigate whether local gastric neurotransmitters modulate acid secretion by regulating basal and gastrin-driven enterochromaffin-like (ECL) cell histamine release. METHODS: The effects of the above agents were investigated in a short-term 90%-95% pure ECL cell culture system. Cells were incubated with either the neuromodulator alone or in combination with gastrin for 10-40 minutes, and histamine secretion was measured by enzyme immunoassay. RESULTS: Acetylcholine, isoproterenol, and vasoactive intestinal polypeptide significantly stimulated basal and gastrin-driven histamine secretion, whereas calcitonin gene-related peptide and somatostatin inhibited basal and gastrin-driven histamine secretion. The M1 muscarinic receptor antagonist pirenzepine dose dependently inhibited the action of acetylcholine, whereas the M3 receptor antagonist 4-diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride had no effect. the rest of the evaluated agents had no effect on ECL cell histamine secretion. CONCLUSIONS: These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.

Acetylcholine↗