Steroid hormones in fish, caution for present and future: A review.

The misuse and overuse of steroid hormones in fish is an emerging problem worldwide. The data on hormonal residue in fish was less due to a lack of effective monitoring programs on hormonal use in fish production. This review revealed the findings of previously published data on different hormonal use and their residue and impact. Steroid hormones were frequently used in fish production to promote growth and reproduction. It was suggested that hormones should be used carefully to ensure environmental, biological, and food safety. The most commonly used steroid hormones in fish production were testosterone, estrogen, progesterone, and cortisol. However, the indiscriminate use left residue in the fish flesh above the FAO/WHO permissible limits. This residue in fish caused many health hazards in consumers, like early puberty in children, advances in bone age, negative repercussions on growth, modification of sexual characteristics, and cancer development such as breast, ovarian, and prostate cancer. It also harmed fish and the aquatic environment. The most common detection methods for these hormones were GC-MS, LC-MS, and UHPLC-MS. Many countries permitted the use of hormones in fish production upon monitoring, whereas many countries prohibited it. Moreover, many countries did not have any rules and regulations on the use of hormones in fish production. Thus, this review is a wake-up call for researchers, policymakers and consumers on the impacts of hormonal residues in food commodities.

Effects of Azadirachta indica on neuropathic pain induced by chronic constriction injury to sciatic nerve of Wistar rat.

Objective: The research was designed to assess the consequences of Azadirachta indica aqueous leaf extract (AILE) on neuropathic pain in Wister rats and the role of the ATP-dependent potassium channel (KATP) as an underlying mechanism. Materials and Methods: This experimental layout was conducted on Wistar rats (n = 120) having 150 to 200 gm of body weight. On the foundation of the experimental design, rats were divided into group I (normal saline, 5 ml/kg/body weight) and group II (sham surgery and treatment with NS), group III [chronic constriction injury (CCI) in the sciatic nerve; and treated with NS], group IV (CCI and treated with AILE 400 mg/kg body weight), Group V (CCI, pretreated with Glibenclamide 15 mg/kg followed by treated with AILE 400 mg/kg). All the treatments were given once daily for a consecutive 21 days via the oral route, except Glibenclamide. Glibenclamide was given once through the intraperitoneal route on the day of the experiment. Results: Based on the neuropathic pain evaluation test, all groups were again sub-divided into subgroup "a" (walking tract analysis), "b" (cold tail immersion test), "c" (Von Frey test), and "d" (hot plate test). AILE showed a significantly higher sciatic functional index (p < 0.05) in walking track analysis, tail flick latency (p ≤ 0.05) in the cold tail immersion test, and paw withdrawal threshold (p ≤ 0.05) in the Von Frey test compared to CCI control. In addition, a nonsignificant difference in all these above-mentioned variables between the rats with CCI plus AILE and the CCI plus AILE plus glibenclamide group indicated that the KATP channel was not involved in the beneficial analgesic effects of AILE. Conclusions: The outcome of the present study indicates that AILE prevented worsening of neuropathic pain after chronic constriction injury in the sciatic nerve of Wistar rats in which the KATP channel was not involved.

Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.

In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM- 10 µM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.

Effects of dexamethasone on the morphometry and biometry of immune organs of broiler chicken / Efectos de la dexametasona en la morfometría y biometría de los Órganos Inmunes del pollo de engorde

The study was conducted to examine the histological changes i.e. morphology and biometry of immune organs (thymus, spleen and bursa cloacalis or «Fabricius¼) of broilers in response to dietary dexamethasone (DEX). The day old chicks were obtained from the commercial hatchery and randomly divided into two groups i.e. control and experimental or treated group. The control group was reared on commercial broiler ration and the experimental group (n=25) was maintained on commercial broiler ration with corticosteroid (Dexamethasone-Decason, BP 0.5 mg, Opsonin @ 7 mg/kg feed). Samples (bursa cloacalis, spleen, and thymus) were collected from the ten control and ten experimental broilers at 14 and 28 days of experiment; then tissues were stained with Hematoxylin and Eosin. The biometric measurements of the samples were performed by the calibrated stage micrometer. Finally, the obtained data were analyzed using GraphPad Prism 8 software. In DEX treated group, the morphology of thymus, spleen and bursa cloacalis did not show any abnormal alterations. But their development rate was slower on visual inspection in DEX treated group. The length and width of bursal follicle of bursa cloacalis, thymic lobule of thymus and white pulp of spleen were statistically consisted but numerically decreased in DEX treated group than the control. The present findings suggested that DEX does not affect the histological architectures of immune organs except causing developmental arrest. Numerical decrease in the biometry of immune organs indicates that DEX causes apoptosis of immune cells in lymphoid organs of broiler.

El estudio se realizó para examinar los cambios histológicos, es decir, la morfología y la biometría de los órganos inmunes (timo, bazo y bolsa cloacal) de pollos de engorde en respuesta a la dexametasona en la dieta (DEX). Los pollitos de un día se obtuvieron de un criadero comercial y se dividieron aleatoriamente en dos grupos, control y experimental. El grupo control se crió con una ración comercial de pollos de engorde y el grupo experimental (n = 25) se mantuvo con una ración comercial de pollos de engorde con corticosteroides (DexamethasoneDecason, BP 0,5 mg, Opsonin @ 7 mg/kg). Se recogieron muestras (bolsa cloacal, bazo y timo) de los diez pollos del grupo control y diez del grupo de engorde experimental, a los 14 y 28 días de experimento. Luego, los tejidos se tiñeron con hematoxilina y eosina. Las mediciones biométricas de las muestras fueron realizadas con un micrómetro calibrado. Finalmente, los datos obtenidos se analizaron utilizando el software GraphPad Prism 8. En el grupo tratado con DEX, la morfología del timo, el bazo y la bolsa cloacal no mostraron alteraciones anormales. Pero su tasa de desarrollo fue más lenta en la inspección visual en el grupo tratado con DEX. La longitud y el ancho del folículo bursal de la bolsa cloacal, el lóbulo tímico del timo y la pulpa blanca del bazo fueron estadísticamente consistentes, pero disminuyeron numéricamente en el grupo tratado con DEX en relación al control. Los hallazgos actuales sugirieron que DEX no afecta la arquitectura histológica de los órganos inmunes, excepto que causa una detención del desarrollo. La disminución numérica en la biometría de los órganos inmunes indica que DEX provoca apoptosis de las células inmunes en los órganos linfoides de los pollos de engorde.

Effect of dipeptidyl peptidase-4 inhibition on circadian blood pressure during the development of salt-dependent hypertension in rats.

A growing body of evidence has indicated that dipeptidyl peptidase-4 (DPP-4) inhibitors have antihypertensive effects. Here, we aim to examine the effect of vildagliptin, a DPP-4-specific inhibitor, on blood pressure and its circadian-dipping pattern during the development of salt-dependent hypertension in Dahl salt-sensitive (DSS) rats. DSS rats were treated with a high-salt diet (8% NaCl) plus vehicle or vildagliptin (3 or 10 mg kg(-1) twice daily by oral gavage) for 7 days. Blood pressure was measured by the telemetry system. High-salt diet for 7 days significantly increased the mean arterial pressure (MAP), systolic blood pressure (SBP) and were also associated with an extreme dipping pattern of blood pressure in DSS rats. Treatment with vildagliptin dose-dependently decreased plasma DPP-4 activity, increased plasma glucagon-like peptide 1 (GLP-1) levels and attenuated the development of salt-induced hypertension. Furthermore, vildagliptin significantly increased urine sodium excretion and normalized the dipping pattern of blood pressure. In contrast, intracerebroventricular infusion of vildagliptin (50, 500 or 2500 µg) did not alter MAP and heart rate in DSS rats. These data suggest that salt-dependent hypertension initially develops with an extreme blood pressure dipping pattern. The DPP-4 inhibitor, vildagliptin, may elicit beneficial antihypertensive effects, including the improvement of abnormal circadian blood pressure pattern, by enhancing urinary sodium excretion.

Analysis of the amount of tissue sample necessary for mitotic count and Ki-67 index in gastrointestinal stromal tumor sampling.

There are no established opinions concerning whether the amount of tissue affects the accuracy of histological analyses in gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the appropriate amount of tissue sample needed for mitotic count based on the risk classification of GISTs and the Ki-67 index using the following three methods: endoscopic ultrasound-guided fine-needle aspiration (FNA), a novel sampling method called tunneling bloc biopsy (TBB), and biopsy forceps followed by TBB (Bf). Forty-three samples (12 FNA, 17 TBB and 14 Bf) diagnosed as GISTs by immunohistological analysis were utilized. The major and minor axes and overlay area of one piece of specimen (OPS) from the three sampling methods were measured using digital imaging software and were analyzed comparatively regarding the acquisition of histological data. The mean major and minor axes (mm) and overlay areas (mm2) were in the order of TBB > Bf > FNA. The evaluable rates by mitotic count and Ki-67 were, respectively, 75% (9/12) and 83.3% (10/12) for FNA samples, 100% (17/17) and 100% (17/17) for TBB samples, and 100% (14/14) and 100% (14/14) for Bf samples (P>0.05). Three FNA samples were judged unevaluable due to too small specimens in overall diagnosis including mitotic count and Ki-67, calculating the cut-off value for the overlay area of OPS as 0.17 mm2. Comparing the concordance rates between the pre- and post-operative samples, TBB samples was significantly better than FNA (P<0.05). Conclusively, while the amounts of tissues obtained by TBB and Bf are unnecessary for the histological assessment of mitotic count and Ki-67 index, developments of the FNA method are needed to minimize sample error. Considering the technical aspects, as well as the size of the specimens, could help to guide therapeutic planning and improve diagnostic yield for GI subepithelial tumors.

Novel method for the management of stenosis after gastric endoscopic submucosal dissection: mucosal incision with steroid injection contralateral to the severely contracted scar.

The aim of the present report was to investigate the efficacy of local steroid injection and oral administration contralateral to a severe contracted scar of large endoscopic submucosal dissection (ESD) for gastric cancer. Among 254 cases that underwent gastric ESD, seven patients underwent resection of more than three-quarters of the circumference of the stomach. Two patients were excluded because they did not meet curative resection criteria of Japan Gastroenterological Endoscopy Society. Therefore, in five patients, circumferentiality, symptom appearance period, and weight loss period were examined. Effect of a contralateral normal mucosa incision for releasing the stenosis followed by local injection and oral steroids were also examined. Abdominal bloating, vomiting, and loss of appetite appeared 42 days on average after gastric ESD, whereas weight loss >5 kg was observed an average of 52.6 days after gastric ESD. Average contralateral mucosal incision length was 51 mm, whereas the average mucosal incision width was 31 mm. All patients underwent a mucosal incision and were given a local injection of 100 mg triamcinolone acetonide. Two patients received an additional 20 mg oral steroid. In cases combined with oral steroid, there was no re-stenosis after the mucosal incision, but two to three balloon dilatations were necessary in three cases in which oral steroids were not given. This method is considered useful for stenosis after large ESD for gastric cancer.

Novel method to prevent gastric antral strictures after endoscopic submucosal dissection: using triamcinolone.

Endoscopic submucosal dissection (ESD) of large gastric lesions often leads to severe gastric strictures, especially in cases of large ESD in the antrum of the stomach. It has recently been reported that balloon dilation, mucosal incision, and local steroid injections can successfully treat gastric strictures. However, there are some complications with existing methods and decreasing the quality of life. We have developed a novel method to prevent severe gastric strictures that does not involve balloon dilation, mucosal incision, or steroid injections after circumferential ESD. Our original method involves the submucosal injection of a mixed solution composed of triamcinolone acetonide and a general solution of glycerol, hyaluronic acid, and a small amount of indigo carmine and epinephrine during the ESD procedure; this mixture is called a mixed solution of triamcinolone (MST). According to standard ESD procedures, several milliliters of MST are injected into the submucosal layer for the purpose of elevating the submucosa during ESD resulting in prevention of severe strictures. Our method using MST take several advantages such as MST method suppress inflammation in ulcer from initial phase, prevention of stricture without obstructive symptoms, and does not require several ballooning. Therefore, MST method is safe and gentle, shorten the hospitalization duration. Here, we described two cases in which we prevented severe strictures of the gastric antrum after completing a circumferential ESD using MST without any complications.

Evaluation of gastric submucosal tumors using endoscopically visualized features with submucosal endoscopy.

Although the macroscopic characteristics of submucosal tumors (SMTs), such as gastrointestinal stromal tumors (GISTs), have been characterized, the assessment of SMTs by their endoscopically visualized features (EVF; which are observed by endoscopic imaging under direct view) remains unevaluated. The aim of the present study was to investigate the potential of endoscopic diagnostics for SMTs using EVF. The EVF of 26 gastric SMT cases, in which the final pathological diagnosis was obtained by core biopsy using the submucosal endoscopy with mucosal flap method, were retrospectively reviewed. Each type of SMT was classified according to the following five EVF: Color, clarity, shape, tumor coating and solidity. Additionally, the EVF of 13 low-risk GISTs and 13 benign submucosal tumors (BSTs) were comparatively evaluated for the five abovementioned EVF. Similar trends were identified between the low-risk GISTs, granular cell tumors and the schwannoma with regard to EVF. However, while these tumors exhibited cloudy EVF, the leiomyomas tended to exhibit clear EVF. Among SMTs of the heterotopic pancreas type, the EVF demonstrated particularly small nodules of the pancreatic tissue itself. Although the sample size included in the present study is small, a classification system for gastric SMTs was proposed according to the EVF. When compared with the BST group, the GIST group demonstrated a significantly higher frequency of tumors that exhibited a combination of three EVF (white, cloudy and rigid) that are consistent with all gastric GISTs (P<0.05). Gastric SMTs may be classified based on the EVF, which indicates that the EVF possess potential diagnostic value for the differentiation of GISTs from BSTs.

Submucosal tunneling techniques: current perspectives.

Advances in endoscopic submucosal dissection include a submucosal tunneling technique, involving the introduction of tunnels into the submucosa. These tunnels permit safer offset entry into the peritoneal cavity for natural orifice transluminal endoscopic surgery. Technical advantages include the visual identification of the layers of the gut, blood vessels, and subepithelial tumors. The creation of a mucosal flap that minimizes air and fluid leakage into the extraluminal cavity can enhance the safety and efficacy of surgery. This submucosal tunneling technique was adapted for esophageal myotomy, culminating in its application to patients with achalasia. This method, known as per oral endoscopic myotomy, has opened up the new discipline of submucosal endoscopic surgery. Other clinical applications of the submucosal tunneling technique include its use in the removal of gastrointestinal subepithelial tumors and endomicroscopy for the diagnosis of functional and motility disorders. This review suggests that the submucosal tunneling technique, involving a mucosal safety flap, can have potential values for future endoscopic developments.

An effective and safe gastric endoscopic submucosal dissection in the right lateral position using an inverted overtube.

Previously, we reported the efficacy of a newly developed inverted overtube in shortening the hemostatic time and obtaining a clear endoscopic view in emergency endoscopic hemostasis. This device also helped us to perform gastric endoscopic submucosal dissection (ESD) more safely by changing the direction of gravity in the right lateral position. To perform a safe ESD, it is important to make an appropriate angle and distance between the electric knife and the gastric mucosa. In this position, the distance to gastric mucosa is reduced, and the angle of the electric knife changes from vertical to somewhat oblique, facilitating safer cutting.

Esophageal anthracosis with tuberculous lymphadenitis confirmed on transesophageal endoscopic ultrasound-guided fine-needle aspiration.

Esophageal anthracosis with tuberculous lymphadenitis is a very rare disease. Almost all reported cases are diagnosed using multiple endoscopic biopsies or thoracic esophagectomy. The present case report describes a case of esophageal anthracosis with tuberculous lymphadenitis that was diagnosed using transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) alone. After taking antituberculosis drugs, the patient's chest pain was relieved and she recovered. The patient achieved an excellent outcome following the use of less invasive methods than mediastinoscopy. If no esophageal anthracotic lesions are found on the mucous membrane layer of the esophagus, transesophageal endoscopic ultrasound-guided fine-needle aspiration is a suitable approach for diagnosing esophageal anthracosis.

Feasibility of pure EFTR using an innovative new endoscopic suturing device: the Double-arm-bar Suturing System (with video).

BACKGROUND: Endoscopic full-thickness resection (EFTR) requires a reliable full-thickness suturing device and an endoscopic counter-traction device to prevent the collapse of the digestive tract. OBJECTIVE: The present study aimed to assess the reliability of newly developed flexible endoscopy suturing devices and the feasibility of pure EFTR. METHODS: A total of 30 EFTRs were performed and allocated to three groups (N = 10 for each group). The full-thickness sutures were placed using over-the-scope clips (OTSCs), hand-sewn sutures, or the Double-arm-bar Suturing System (DBSS). Air leak tests were conducted in the three groups. The times required for the placement of one OTSC suture and single-stitch simple interrupted sutures (hand-sewn and DBSS sutures, respectively) were also compared. RESULTS: All 30 full-thickness sutures were completely and successfully placed. Regarding the air leak tests, the Mann-Whitney U test showed significant differences between OTSC and hand-sewn sutures (p = 0.003). There was also a significant difference between OTSC and DBSS sutures (p = 0.023). There was no significant difference between hand-sewn and DBSS sutures (p = 0.542). A significant difference was found in the suture time for single-stitch simple interrupted sutures among the OTSC, hand-sewn, and DBSS sutures. The Mann-Whitney U test revealed a significant difference between OTSC and hand-sewn sutures (p = 0.0001). There was no significant difference between OTSC and DBSS sutures (p = 0.533), while a significant difference was found between hand-sewn and DBSS sutures (p = 0.0001). CONCLUSIONS: Pure EFTR is feasible if the mechanical counter traction system is used to expand a small operative field and DBSS is used to make full-thickness sutures. The high safety of full-thickness resection and full-thickness suturing allows for clinical applications of this method.

Radical excision of Barrett's esophagus and complete recovery of normal squamous epithelium.

To treat Barrett's esophagus (BE), radiofrequency ablation or cryotherapy are effective treatments for eradicating BE with dysplasia and intestinal metaplasia, and reduce the rates of Barrett's esophageal adenocarcinoma (BAC). However, patients with BE and dysplasia or early cancer who achieved complete eradication of intestinal metaplasia, BE recurred in 5% within a year, requiring expensive endoscopic surveillances. We performed endoscopic submucosal dissection as complete radically curable treatment procedure for BE with dysplasia, intestinal metaplasia and BAC.

Effects of gastric irrigation on bacterial counts before endoscopic submucosal dissection: a randomized case control prospective study.

OBJECTIVE: The antiseptic effect of gastric irrigation before endoscopic submucosal dissection (ESD) has not yet been reported. The aim of the randomized prospective study is to evaluate the antiseptic effects of gastric irrigation of saline solution before ESD by evaluating bacterial count. METHODS: This prospective randomized controlled trial included 50 patients diagnosed with early gastric cancer who were randomly divided into 2 groups (25 patients in each group) by using the opaque envelope method: the clean group (irrigation with 2 L saline solution before ESD) and the regular group (no irrigation). The gastric juice was collected and cultured before ESD. The entire stomach was irrigated using a water jet attached to an endoscope. After ESD with resection and removal of the tumor specimen, a postoperative culture of the gastric juice was obtained using the same method as the preoperative culture. RESULTS: The mean log bacterial count of the post-gastric irrigation gastric juice was 5.08±0.75 in the regular group and 1.86±0.86 in the clean group. The difference in the bacterial counts was significant between the groups (P = 0.0004). The difference in the white blood cells (WBC) count on POD 1 was significant (P = 0.044). WBC count on POD 2 did not significantly differ between the groups (P = 0.3). The difference in the body temperature (BT) on POD 1 was significant (P = 0.017), On POD 2 the BT was not significant between the groups (P = 0.5). On POD 1, 88% of the patients in the regular group and 16% of the patients in the clean group had mild to moderate spontaneous pain (P = 0.0026). On POD 2 the proportion with mild to moderate spontaneous pain was 36% and 24% in the regular group and the clean group, respectively (P = 0.1). CONCLUSION: Pre-ESD gastric irrigation with saline solution is effective and feasible for suppressing infection during the ESD procedure with favorable clinical outcomes. TRIAL REGISTRATION INFORMATION: The university hospital medical information network (UMIN) #000008691.