Comparisons Between Endoscopic Band Ligation, Radiofrequency Ablation and Endoscopic Thermal Therapy for Gastric Antral Vascular Ectasia: A Meta-Analysis.

BACKGROUND: Endoscopic band ligation (EBL) and radiofrequency ablation (RFA) have emerged as alternative therapies of gastric antral vascular ectasia (GAVE) in addition to endoscopic thermal therapy (ETT), but the optimum choice remains inconclusive. AIM: We conducted a meta-analysis in order to compare these three treatments for GAVE. METHODS: We searched the electronic databases of PubMed, Embase and Cochrane Central Register of Controlled Trials without any language restrictions and also performed a manual literature search of bibliographies located in both retrieved articles and published reviews for eligible publications prior to December 8, 2021. We included comparative trials which had evaluated the efficacy and safety of interventions in adults (aged ≥ 18 years) diagnosed with symptomatic GAVE and was confirmed according to clinical backgrounds and upper gastrointestinal endoscopy. We included reports that compared three interventions, ETT, EBL, and RFA. The study was comprised of adults diagnosed with GAVE and focused on overall mortality, bleeding cessation, endoscopic improvement, complications, hospitalization, hemoglobin improvement, number of sessions and transfusion requirements. RESULTS: Twelve studies were performed involving a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation (OR 4.48, 95% CI 1.36-14.77, p = 0.01), higher hemoglobin improvement (MD 0.57, 95% CI 0.31-0.83, p < 0.01) and lower number of sessions (MD - 1.44, 95% CI - 2.54 to - 0.34, p = 0.01). Additionally, EBL was superior to ETT in endoscopic improvement (OR 6.00, 95% CI 2.26-15.97, p < 0.01), hospitalization (MD - 1.32, 95% CI - 1.91 to - 0.74, p < 0.01) and transfusion requirement (MD - 2.66, 95% CI - 4.67 to - 0.65, p = 0.01) with statistical significance, with the exception of mortality (OR 0.58, 95% CI 0.19-1.77, p = 0.34) and complication rate (OR 5.33, 95% CI 0.58-48.84, p = 0.14). CONCLUSION: For GAVE, we suggest that EBL be initially recommended, and APC and RFA be used as alternative treatment choices based upon a very low quality of evidence.

Does the level of inferior mesenteric artery ligation affect short-term and long-term outcomes of patients with sigmoid colon cancer or rectal cancer? A single-center retrospective study.

BACKGROUND: For sigmoid colon or rectal cancer, a definite consensus regarding the optimal level ligating the inferior mesenteric artery (IMA) has not been reached. We performed this study to determine whether the ligation level significantly affected short-term and long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery. METHODS: Medical records of patients with sigmoid colon or rectal cancer who had undergone curative laparoscopic surgery between January 2008 and December 2014 at the Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Traditional Chinese Medicine were reviewed. Then, the high tie group (HTG) was compared with the low tie group (LTG) in terms of short-term and long-term outcomes. RESULTS: Five-hundred ninety patients were included. No significant differences between two groups regarding baseline characteristics existed. HTG had a significantly higher risk of anastomotic fistula than LTG (21/283 vs 11/307, P = 0.040). Additionally, high ligation was proven by multivariate logistic regression analysis to be an independent factor for anastomotic fistula (P = 0.038, OR = 2.232, 95% CI: 1.047-4.758). Furthermore, LT resulted in better preserved urinary function. However, LTG was not significantly different from HTG regarding operative time (P = 0.075), blood transfusion (P = 1.000), estimated blood loss (P = 0.239), 30-day mortality (P = 1.000), ICU stay (P = 0.674), postoperative hospital stay (days) (P = 0.636), bowel obstruction (P = 0.659), ileus (P = 0.637), surgical site infection (SSI) (P = 0.121), number of retrieved lymph nodes (P = 0.501), and number of metastatic lymph nodes (P = 0.131). Subsequently, it was revealed that level of IMA ligation did not significantly influence overall survival (OS) (P = 0.474) and relapse-free survival (RFS) (P = 0.722). Additionally, it was revealed that ligation level did not significantly affect OS (P = 0.460) and RFS (P = 0.979) of patients with stage 1 cancer, which was also observed among patients with stage 2 or stage 3 cancer. Ultimately, ligation level was not an independent predictive factor for either OS or RFS. CONCLUSIONS: HT resulted in a significantly higher incidence of anastomotic fistula and worse preservation of urinary function. Level of IMA ligation did not significantly affect long-term outcomes of patients with sigmoid colon or rectal cancer after curative laparoscopic surgery.

Variceal Bleeding: Beyond Banding.

Despite advances in the management of complications of portal hypertension, variceal bleeding continues to be associated with significant morbidity and mortality. While endoscopic variceal band ligation remains first line therapy for treating bleeding and high-risk non-bleeding esophageal varices, alternate therapies have been explored, particularly in cases of refractory bleeding. The therapies being explored include stent placement, hemostatic powder use, over-the-scope clips and others. For gastric variceal bleeding, endoscopic ultrasound-guided therapies have recently emerged as promising interventions for hemostasis. The aim of this article is to highlight these alternative therapies and their potential role in the management of gastric and esophageal variceal bleeding.

The use of topical anaesthetic in the banding of internal haemorrhoids: a feasibility study for a randomised control trial.

INTRODUCTION: Rubber band ligation (RBL) is a procedure commonly performed in colorectal clinics for internal haemorrhoids. Overall, 90% of patients experience pain following RBL. We aimed to complete a feasibility randomised control trial assessing the role of topical anaesthetic before RBL of internal haemorrhoids. METHODS: We performed a prospective, single-centre, single blinded, randomised (1:1) control feasibility trial. Patients presenting with symptomatic haemorrhoids suitable for banding were randomised to undergo the procedure with local anaesthetic or without (control). Pain scores and vasovagal symptoms were assessed at 0 minutes, 30 minutes, 4 hours and 72 hours after the procedure. Primary outcome measures were recruitment rate, participant retention rate and patient and surgeon acceptability. Secondary outcome measures were pain scores up to 72 hours, vasovagal episodes, new use of analgesia and adverse outcomes. RESULTS: In total, 35 patients (18 topical anaesthetic, group A; 17 no anaesthetic gel, group B) were recruited. Mean recruitment rate was 11.7 participants per month. Thirty-three (94%) participants remained in the study until completion, with two patients lost to telephone follow-up. The treatment was acceptable for 35 (97%) eligible patients. One patient declined enrolment. The treatment was acceptable to all surgeons (100%). There was a significant difference in median pain scores of -2 (95% CI -4.0 to -1.0, p=0.0006) at the 30-minute time point only. There was no significant difference in vasovagal symptoms (p=0.10) or new analgesia use (p=0.85). CONCLUSION: We have shown that a phase III clinical trial is feasible for assessing the role of topical anaesthetic before RBL of internal haemorrhoids. We have demonstrated excellent patient recruitment and retention as well as patient and surgeon acceptability.

Electroacupuncture attenuates vascular hyporeactivity in a rat model of portal hypertension induced by bile duct ligation.

BACKGROUND: A hyperdynamic circulation and impaired vascular responsiveness to vasoconstrictors are observed in portal hypertension (PHT) rats. Inflammation is a major contributor to the hyperdynamic circulation state in murine models of PHT. Electroacupuncture (EA) may ameliorate the inflammatory response and limit arterial vasodilatation and portal pressure. This study investigated the possible mechanisms underlying putative hemodynamics effects of EA in normal and PHT rats. METHODS: PHT was induced by bile duct ligation (BDL) surgery over 4 weeks in rats. Sham-operated and BDL rats were treated with low-frequency EA (2 Hz) at ST36 10 min three times weekly for one or two consecutive weeks (for a total of 3 or 7 treatments, respectively). Serum tumor necrosis factor-α (TNF-α), nitrite/nitrate (NOx) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were analyzed, and hemodynamic variation and contractile responses to phorbol-12,13-dibutyrate and phenylephrine in aortic and superior mesenteric arterial rings were recorded. Inducible (i) and endothelial (3) nitric oxide synthase (NOS), cyclooxygenase-1 (COX-1), and protein kinase C-α (PKC-α) levels were determined by Western blotting. RESULTS: EA significantly reduced portal pressure and serum TNF-α, NOx and 6-keto-PGF1α levels compared to the untreated BDL group, enhanced maximum contractile responses in the aorta, up-regulated PKC-α, and down-regulated iNOS and COX-1 levels. In addition, EA decreased the aortic angiogenesis signaling cascade, reflected by down-regulation of vascular endothelial growth factor (VEGF) abundance and transforming growth factor ß receptor (TGFßR)I/II expression, as assessed by immunostaining. CONCLUSION: EA attenuates TNF-α, NO and 6-keto-PGF1α overproduction, modulates the vascular levels of constitutive NOS and PKC-α, blunts the development of the angiogenesis cascade, and enhances vascular contractile force in PHT rats.

Clinical study of herbal mixture "Diding Oral Medicine" as an alternative to preventative antibiotics in perioperative hemorrhoids: A CARE-compliant article.

ABSTRACT: To study the clinical effects of Diding Oral Medicine as an alternative to preventative antibiotics in perioperative hemorrhoids.From August 2017 to February 2018, a total of 214 patients who were treated with external exfoliation and internal ligation of mixed hemorrhoids in our hospital were divided into the control group and experimental group by way of stratified random (107 cases in each group). Patients in the control group were given antibiotics preventatively before operation, while patients in the experimental group took Diding Oral Medicine before operation, and the white blood cell count, neutrophil count, wound recovery, pain score, anal bulge score, and pathogen culture of wound secretions were compared between the 2 groups.There was no significant difference in white blood cell count and neutrophil count between both groups before and after operation (P > .05). The wound seepage score, wound edema score, and wound area score in the experimental group were lower than those in the control group, and the wound healing in the experimental group was shorter than that in the control group (all P < .05). The pain score and anal bulge score of the experimental group were decreased significantly compared to the control group (P < .05). In addition, the detection rate of pathogenic bacteria in the experimental group was downregulated significantly compared to the control group (P < .05).The Diding Oral Medicine has prominent bacteriostatic and antibacterial effects on patients with hemorrhoids during perioperative period, and promotes wound healing, reduces pain stress, and anal bulge.

Electroacupuncture improves neuronal plasticity through the A2AR/cAMP/PKA signaling pathway in SNL rats.

Improvements in neuronal plasticity are considered to be conducive to recovery from neuropathic pain. Electroacupuncture (EA) is regarded as an effective rehabilitation method for neuropathic pain. However, the effects and potential mechanism associated with EA-induced repair of hyperesthesia are not fully understood. Evidence has suggested that the adenosine A2A receptor (A2AR) and the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway play an important role in improving neuropathic pain. Here, we examined the function of EA in promoting neuronal plasticity in spinal nerve ligation (SNL) rats. The A2AR antagonist SCH58261, A2AR agonist 2-p-(2-carboxyethyl)phenethylamino-50-N-ethylcarboxamido adenosine HCl (CGS21680) and A2AR siRNA were used to confirm the relationship between A2AR and the cAMP/PKA pathway as well as the effects of A2AR on EA-induced improvements in neurobehavioral state and neuronal plasticity. Mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), HE staining, Western blotting, RT-PCR, immunofluorescence, enzyme-linked immunosorbent assay, Nissl staining, silver staining, Golgi-Cox staining and transmission electron microscopy were used to evaluate the changes in neurobehavioral performance, protein expression, neuronal structure and dendrites/synapses. The results showed that EA and CGS21680 improved the behavioral performance, neuronal structure and dendritic/synaptic morphology of SNL rats, consistent with higher expression levels of A2AR, cAMP and PKA. In contrast to the positive effects of EA, SCH58261 inhibited dendritic growth and promoted dendritic spine/synaptic remodeling. In addition, the EA-induced improvement in neuronal plasticity was inhibited by SCH58261 and A2AR siRNA, consistent with lower expression levels of A2AR, cAMP and PKA, and worse behavioral performance. These results indicate that EA suppresses SNL-induced neuropathic pain by improving neuronal plasticity via upregulating the A2AR/cAMP/PKA signaling pathway.

Bromelain reduced pro-inflammatory mediators as a common pathway that mediate antinociceptive and anti-anxiety effects in sciatic nerve ligated Wistar rats.

The involvement of pro-inflammatory mediators complicates the complex mechanism in neuropathic pain (NP). This study investigated the roles of bromelain against pro-inflammatory mediators as a mechanism that underpins its antinociceptive and anti-anxiety effects in the peripheral model of NP. Sixty-four male Wistar rats randomly divided into eight groups, were used for the study. A chronic constriction injury model of peripheral neuropathy was used to induce NP. Tail-immersion and von Frey filaments tests were used to assess hyperalgesia while open field and elevated plus mazes were used to assess anxiety-like behaviour. NF-кB, iNOS, nitrate, and pro-inflammatory cytokines were investigated in the plasma, sciatic nerve, and brain tissues using ELISA, spectrophotometer, and immunohistochemistry techniques after twenty-one days of treatment. Bromelain significantly (p < 0.05) improved the cardinal signs of NP and inhibited anxiety-like behaviours in ligated Wistar rats. It mitigated the increases in cerebral cortex interleukin (IL) -1ß, IL-6, and PGE2 levels. Bromelain reduced NF-кB, IL-1ß, IL-6, TNF-α, PGE2, and nitrate concentrations as well as the expression of iNOS in the sciatic nerve. Hence, the antinociceptive and anxiolytic effects of bromelain in the sciatic nerve ligation model of NP is in part due to its ability to reduce nitrosative and inflammatory activities.

Delayed Umbilical Cord Clamping After Birth: ACOG Committee Opinion, Number 814.

Delayed umbilical cord clamping appears to be beneficial for term and preterm infants. In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes. There is a small increase in the incidence of jaundice that requires phototherapy in term infants undergoing delayed umbilical cord clamping. Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed umbilical cord clamping in term infants should ensure that mechanisms are in place to monitor and treat neonatal jaundice. In preterm infants, delayed umbilical cord clamping is associated with significant neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage. Delayed umbilical cord clamping was not associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor was it associated with a difference in postpartum hemoglobin levels or the need for blood transfusion. Given the benefits to most newborns and concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. The ability to provide delayed umbilical cord clamping may vary among institutions and settings; decisions in those circumstances are best made by the team caring for the mother-infant dyad.

Delayed Umbilical Cord Clamping After Birth: ACOG Committee Opinion Summary, Number 814.

Delayed umbilical cord clamping appears to be beneficial for term and preterm infants. In term infants, delayed umbilical cord clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcomes. There is a small increase in the incidence of jaundice that requires phototherapy in term infants undergoing delayed umbilical cord clamping. Consequently, obstetrician-gynecologists and other obstetric care providers adopting delayed umbilical cord clamping in term infants should ensure that mechanisms are in place to monitor and treat neonatal jaundice. In preterm infants, delayed umbilical cord clamping is associated with significant neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, decreased need for blood transfusion, and lower incidence of necrotizing enterocolitis and intraventricular hemorrhage. Delayed umbilical cord clamping was not associated with an increased risk of postpartum hemorrhage or increased blood loss at delivery, nor was it associated with a difference in postpartum hemoglobin levels or the need for blood transfusion. Given the benefits to most newborns and concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. The ability to provide delayed umbilical cord clamping may vary among institutions and settings; decisions in those circumstances are best made by the team caring for the mother-infant dyad.

Soluble guanylyl cyclase stimulation and phosphodiesterase-5 inhibition improve portal hypertension and reduce liver fibrosis in bile duct-ligated rats.

BACKGROUND: In cirrhosis, the nitric oxide-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway is impaired, which contributes to increased intrahepatic vascular resistance (IHVR) and fibrogenesis. We investigated if sGC stimulation (riociguat (RIO)), sGC activation (cinaciguat (CINA)) or phosphodiesterase (PDE)-5 inhibition (tadalafil (TADA)) improves portal hypertension (PHT) and liver fibrosis. METHODS: Fifty male Sprague-Dawley rats underwent bile-duct ligation (BDL) or sham operation. RIO (0.5 mg/kg), CINA (1 mg/kg), TADA (1.5 mg/kg) or vehicle (VEH) was administered from weeks 2 to 4 after BDL. At week 4, invasive haemodynamic measurements were performed, and liver fibrosis was assessed by histology (chromotrope-aniline blue (CAB), Picro-Sirius red (PSR)) and hepatic hydroxyproline content. RESULTS: Cirrhotic bile duct-ligated rats presented with PHT (13.1 ± 1.0 mmHg) and increased IHVR (4.9 ± 0.5 mmHg⋅min/mL). Both RIO (10.0 ± 0.7 mmHg, p = 0.021) and TADA (10.3 ± 0.9 mmHg, p = 0.050) decreased portal pressure by reducing IHVR (RIO: -41%, p = 0.005; TADA: -21%, p = 0.199) while not impacting heart rate, mean arterial pressure and portosystemic shunting. Hepatic cGMP levels increased upon RIO (+239%, p = 0.006) and TADA (+32%, p = 0.073) therapy. In contrast, CINA dosed at 1 mg/kg caused weight loss, arterial hypotension and hyperlactataemia in bile duct-ligated rats. Liver fibrosis area was significantly decreased by RIO (CAB: -48%, p = 0.011; PSR: -27%, p = 0.121) and TADA (CAB: -21%, p = 0.342; PSR: -52%, p = 0.013) compared to VEH-treated bile duct-ligated rats. Hepatic hydroxyproline content was reduced by RIO (from 503 ± 20 to 350 ± 30 µg/g, p = 0.003) and TADA (282 ± 50 µg/g, p = 0.003), in line with a reduction of the hepatic stellate cell activation markers smooth-muscle actin and phosphorylated moesin. Liver transaminases decreased under RIO (AST: -36%; ALT: -32%) and TADA (AST: -24%; ALT: -27%) treatment. Hepatic interleukin 6 gene expression was reduced in the RIO group (-56%, p = 0.053). CONCLUSION: In a rodent model of biliary cirrhosis, the sGC stimulator RIO and the PDE-5 inhibitor TADA improved PHT. The decrease of sinusoidal vascular resistance was paralleled by a reduction in liver fibrosis and hepatic inflammation, while systemic haemodynamics were not affected.

Efficacy of Shenfu decoction on sepsis in rats with condition induced by cecal ligation and puncture.

OBJECTIVE: To evaluate the efficacy of Shenfu decoction (SFD) prepared with a traditional Chinese formula, on sepsis in rats with the condition induced by cecal ligation and puncture (CLP), and to study the possible mechanism underlying its action. METHODS: Forty clean-grade male Sprague-Dawley rats were divided randomly into three groups: normal control group (NCG, n = 10), model control group (MCG, n = 15) and Shenfu decoction group (SFDG, n = 15). Sham-operated rats in NCG were served as operation control, while rats in both MCG and SFDG were exposed to CLP, a procedure to develop experimental sepsis. Rats in SFDG were administered with SFD by gavage (3 mg/g of body weight, twice a day) 2 h prior to CLP and directly after successful CLP, while rats in NCG and MCG were gavaged with equivalent volume of sterilized water. Rats in all groups were starved with free access to drink. After 24 h of administration, the mortality of rats in each group was assessed. The indicators of inflammatory response [the peritoneal inflammation by Simon's method Classification as well as serum concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme linked immunosorbent assay (ELISA)] in survival rats were evaluated. The indicators of gut barrier [The intestinal mucosal injury index, serum concentrations of D-lactic acid and secretory IgA (sIgA) in intestinal mucosa by ELISA, as well as gut microbiota by16S rRNA gene sequencing] in survival rats were evaluated. RESULTS: The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (P < 0.01). The mortality (20%) of rats in SFDG was lower than that (33.3%) of the MCG (χ2 = 6.533, P = 0.011). Compared with the MCG,the peritoneal inflammation as well as serum concentrations of TNF-α and IL-6 decreased significantly in SFDG (all P < 0.01). Compared with the MCG, the IMII, serum concentrations of D-lactic acid, sIgA in intestinal mucosa were alleviated by SFD treatment (all P < 0.01). Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. Increase in levels of Proteobacteria and reduction levels of Bacteroidetes induced by sepsis were observed, and these two disturbed gut microbiota phyla could be regulated after SFD treatment. CONCLUSION: SFD may play a protective role in sepsis by alleviating sepsis-induced inflammatory response and gut barrier damage in rats.

Effect of photobiomodulation therapy as an adjunct to scaling and root planing in a rat model of ligature-induced periodontitis: a histological and radiographic study.

This study aimed to histologically and radiographically evaluate the effectiveness of low-intensity laser irradiation of different wavelengths (660 or 808 nm) as an adjunct to scaling and root planing in the treatment of experimental periodontitis in rats. Periodontitis was induced by placing a ligature around the mandibular first molar of the rats. In total, 40 Wistar rats were randomly divided into five groups (n = 8 each): control (CG), periodontal disease (PD), scaling and root planing (SRP), SRP + 660 nm laser (GL660) and SRP + 808 nm laser (GL808). Groups with laser use received radiation at 6 points in the first molar. The animals were euthanized at baseline and at 7 and 14 days after the interventions. Mandibles were surgically removed for histomorphometric and radiographic assessment of periodontal tissues. The GL660 group showed lesser bone loss than the PD group (P < 0.05) and greater alveolar bone margin after 14 days, indicating a better long-term treatment response (P < 0.05). These findings suggest that SRP with the 660 nm laser as an adjunct results in more favorable radiographic and histological responses than the 808 nm laser.

Shenqi Fuzheng Injection impairs bile duct ligation-induced cholestatic liver injury in vivo.

BACKGROUND AND AIM: The aim of the present study sought to determine the protective function of Shenqi Fuzheng Injection (SFI) in cholestatic liver injury. METHODS: Cholestatic liver injury was induced in a 7-day bile duct-ligated (BDL) rat model. Rats were divided into three groups that were comprised of: (1) Sham; (2) BDL model; and (3) SFI treatment. The sham and BDL groups were treated with an appropriate volume of 0.9% sodium chloride as the vehicle, and the SFI group was administered SFI at a dose of 20 ml/kg/day, via tail vein injection. RESULTS: SFI significantly (all at P<0.01) decreased the levels of serum aspartate aminotransferase and alanine aminotransferase as compared with the BDL group, which was associated with reduced severity of inflammatory cell infiltration and hepatic damage. Moreover, SFI significantly decreased the levels of hepatic interleukin-6 (P<0.01), tumor necrosis factor-α (P=0.041), and malondialdehyde (P=0.026), and significantly increased the levels of total superoxide dismutase (P<0.01), and the GSH/GSSG ratio (P=0.041) in the liver. Western blot analysis showed that SFI increased PPAR-γ expression; however, SFI treatment decreased cyclooxygenase-2 (COX-2) expression and the phosphorylation of NF-κBp65. CONCLUSIONS: These data demonstrated that SFI attenuated both inflammation and oxidative stress, and disrupted cholestatic liver injury. The involved mechanism was dependent, at least in part, on regulating PPAR-γ, COX-2, and NF-κBp65 expression.

Development and use of a mouth gag for oral experiments in rats.

OBJECTIVE: Rodent models such as mice and rats are often used in investigations of the oral cavity in the fields of periodontology and dental anesthesiology. When various treatments are performed in the oral cavity, it is very important to secure the visual field while keeping the animal's mouth fully opened, in order to ensure the consistency of experimental procedures. Therefore, we developed a standardized gag conforming to various degrees of oral cavity size of different aged rats. DESIGN: The gag was composed of a rectangular incisor-opening frame constructed from a stainless steel wire with retractors and a dial to alter the opening amounts. Wistar rats (n = 5) aged 4, 8, and 12 weeks were used to evaluate the suitability of the gag in oral cavity. As tests for application of gag in intraoral experiments, the ligature placement around the molars, drug injection into the gingiva, measurement of gingival blood flow rate, and installation of stimulation an electrode for somatosensory-evoked potentials into the molar were performed. RESULTS: Adjusting the opening dial enabled both the maintenance of open state and more favorable intraoral observation compared with tweezers as a control device in all different types of rats. Furthermore, our gag made it possible to facilitate the insertion of diverse instruments into the oral cavity and to achieve various experimental purposes. The stainless-steel gag can also be autoclaved and dry-heat sterilized. CONCLUSION: It was revealed that our mouth gag can be widely applied to various oral experiments in different old aged rats.

Sodium tanshinone IIA sulfonate attenuates cardiac dysfunction and improves survival of rats with cecal ligation and puncture-induced sepsis.

Cardiac dysfunction, a common consequence of sepsis, is the major contribution to morbidity and mortality in patients. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of Tanshinone IIA (TA), a main active component of Salvia miltiorrhiza Bunge, which has been widely used in China for the treatment of cardiovascular and cerebral system diseases. In the present study, the effect of STS on sepsis-induced cardiac dysfunction was investigated and its effect on survival rate of rats with sepsis was also evaluated. STS treatment could significantly decrease the serum levels of C-reactive protein (CRP), procalcitonin (PCT), cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), and brain natriuretic peptide (BNP) in cecal ligation and puncture (CLP)-induced) septic rats and improve left ventricular function, particularly at 48 and 72 h after CLP. As the pathogenesis of septic myocardial dysfunction is attributable to dysregulated systemic inflammatory responses, several key cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10) and high mobility group protein B1 (HMGB1), were detected to reveal the possible mechanism of attenuation of septic myocardial dysfunction after being treated by STS. Our study showed that STS, especially at a high dose (15 mg·kg-1), could efficiently suppress inflammatory responses in myocardium and reduce myocardial necrosis through markedly reducing production of myocardial TNF-α, IL-6 and HMGB1. STS significantly improved the 18-day survival rate of rats with sepsis from 0% to 30% (P < 0.05). Therefore, STS could suppress inflammatory responses and improve left ventricular function in rats with sepsis, suggesting that it may be developed for the treatment of sepsis.

Proline supplementation mitigates the early stage of liver injury in bile duct ligated rats.

Background Proline is a proteinogenic amino acid with multiple biological functions. Several investigations have been supposed that cellular proline accumulation is a stress response mechanism. This amino acid acts as an osmoregulator, scavenges free radical species, boosts cellular antioxidant defense mechanisms, protects mitochondria, and promotes energy production. The current study was designed to investigate the effect of proline treatment on the liver in bile duct ligated (BDL) rats as an animal model of cholestasis/cirrhosis. Methods BDL rats were supplemented with proline-containing drinking water (0.25% and 0.5% w:v), and samples were collected at scheduled time intervals (3, 7, 14, 28, and 42 days after BDL surgery). Results Drastic elevation in the serum level of liver injury biomarkers and significant tissue histopathological changes were evident in BDL rats. Markers of oxidative stress were also higher in the liver of BDL animals. It was found that proline supplementation attenuated BDL-induced alteration in serum biomarkers of liver injury, mitigated liver histopathological changes, and alleviated markers of oxidative stress at the early stage of BDL operation (3, 7, and 14 days after BDL surgery). Conclusions The hepatoprotection provided by proline in BDL animals might be associated with its ability to attenuate oxidative stress and its consequences.

Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis.

OBJECTIVE: Grape seed proanthocyanidine extract (GSPE) is a strong antioxidant derived from the grape seeds (Vitis vinifera, Terral J.F.) and has a polyphenolic structure with a wide range of biological activity. The aim of the present study was to evaluate the effects of GSPE on alveolar bone loss and histopathological changes in rats with diabetes mellitus and ligature-induced periodontitis. MATERIAL AND METHODS: Forty rats were divided into 6 study groups. Control (C, 6 rats) group, periodontitis (P, 6 rats) group, diabetes (D, 6 rats) group, diabetes and periodontitis (D+P, 6 rats) group, diabetes, periodontitis and 100 mg/kg/day GSPE (GSPE-100, 8 rats), and diabetes, periodontitis and 200 mg/kg/day GSPE (GSPE-200, 8 rats) group. Diabetes mellitus was induced by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Periodontitis was induced via ligation method. Silk ligatures were placed at the mandibular right first molars. GSPE was administered by oral gavage. After 30 days, all rats were killed. Alveolar bone loss was measured morphometrically via a stereomicroscope. For histopathological analyses, Alizarin red staining, and matrix metalloproteinase (MMP)-8, vascular endothelial growth factor and hypoxia inducible factor (HIF)-1α immunohistochemistry were performed. Tartrate-resistant acid phosphatase-positive osteoclast cells and relative total inflammatory cells were also determined. RESULTS: The highest alveolar bone loss was observed in the D+P group (P < .05). GSP-200 group decreased alveolar bone loss (P < .05). The D+P group had the highest osteoclast counts, but the difference was not significant compared to the P, GSPE-100 and GSPE-200 groups (P > .05). The inflammation in the D+P group was also higher than the other groups (P < .05). The osteoblast numbers increased in the GSPE-100 and GSPE-200 groups compared to the P and D+P groups (P < .05). MMP-8 and HIF-1α levels were highest in the D+P group and GSPE significantly decreased these levels (P < .05). CONCLUSION: Within the limits of this animal study, it can be suggested that GSPE administration may decrease periodontal inflammation and alveolar bone loss via decreasing MMP-8 and HIF-1α levels and increase osteoblastic activity in diabetic rats with experimental periodontitis.

Development of Noninvasive in Vivo Approach to Assess Vascular Permeability in Inflammation Using Fluorescence Imaging.

INTRODUCTION: In vivo fluorescence imaging can quantify vascular permeability without requiring sacrifice of animals. However, use of this noninvasive approach for vascular permeability assessment in remote organ injury caused by systemic inflammatory disease has not been reported. METHODS: Evans blue (EB) and Genhance 750 fluorescent dye were mixed and injected into mice. The lung as a remote organ and the footpad as a noninvasive observational site were assessed in a cecal ligation and puncture (CLP)-induced systemic inflammation mouse model and compared with sham and hydrocortisone pretreated (CLP + HC) mouse models. Extraction of EB in harvested tissues was assessed as a conventional indicator of vascular permeability. Fluorescent intensities in the footpad or harvested lung were assessed and their correlation was analyzed to investigate this novel, noninvasive approach for estimation of lung vascular permeability. RESULTS: Fluorescent intensity in the footpad and harvested lung in the CLP group was significantly higher than in the other groups (footpad, sham vs. CLP, P < 0.0001; CLP vs. CLP + HC, P = 0.0004; sham vs. CLP + HC, P = 0.058; lung, sham vs. CLP, P < 0.0001; CLP vs. CLP + HC, P < 0.0001; sham vs. CLP + HC, P = 0.060). The fluorescent intensity in the footpad was strongly correlated with that in the lung (r = 0.95). CONCLUSIONS: This fluorescent technique may be useful for vascular permeability assessment based on EB quantification. Footpad fluorescent intensity was strongly correlated with that in the lung, and may be a suitable indicator in noninvasive estimation of lung vascular permeability.

Tussilagone Inhibits the Inflammatory Response and Improves Survival in CLP-Induced Septic Mice.

Tussilagone, extracted from Tussilago farfara is an oriental medicine used for asthma and bronchitis. We investigated its mechanism of action, its inhibitory effects on lipopolysaccharide-induced inflammation in macrophages, and its impact on viability in a cecal ligation and puncture (CLP)-induced mouse model of sepsis. Tussilagone suppressed the expression of the inflammatory mediators, nitric oxide and prostaglandin E2, and the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 (HMGB1), in lipopolysaccharide-stimulated RAW 264.7 cells and peritoneal macrophages. Tussilagone also reduced the activation of the mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) involved in the activation of various inflammatory mediators in activated macrophages. Moreover, tussilagone administration (1 mg/kg and 10 mg/kg) produced decreased mortality and lung injury in CLP-activated septic mice. Augmented expression of cyclooxygenase (COX)-2 and TNF-α in pulmonary alveolar macrophages of septic mice were attenuated by tussilagone administration. Tussilagone also suppressed the induction of nitric oxide, prostaglandin E2, TNF-α and HMGB1 in the serum of the septic mice. Overall, tussilagone exhibited protective effects against inflammation and polymicrobial sepsis by suppressing inflammatory mediators possibly via the inhibition of NF-κB activation and the MAP kinase pathway. These results suggest the possible use of tussilagone for developing novel therapeutic modalities for sepsis and other inflammatory diseases.