Efficacy of BCG vaccine and Mitomycin C for the treatment of ocular squamous cell carcinoma in bovines.

Bovine ocular squamous cell carcinoma (BOSCC) also called cancer eye, represents the most economically important neoplasm in large animals. Hereditary factors, environmental factors, lack of eyelid pigmentation, age and dietary habits have all been reported to play a role in the etiopathogenesis of bovine ocular squamous cell carcinoma. In group I, six animals with small, localized eye cancer where vision was not affected were included and subjected to intralesional injection of Bacillus Calmette- Guerin (BCG) vaccine at 0, 14, 35, and 56 days interval. In group II (six animals), surgical excision and Mitomycin C 0.04% topically on alternate weeks for two months as adjunctive therapy. All the animals recovered completely with no recurrence for a follow up period of one year.

A Randomized Controlled Trial Comparing Subconjunctival Injection to Direct Scleral Application of Mitomycin C in Trabeculectomy.

PURPOSE: To compare the efficacy of intraoperative scleral application with subconjunctival injection of mitomycin C (MMC) in trabeculectomy. DESIGN: Prospective, randomized, interventional study. METHODS: This study took place in a single clinical practice in an academic setting. Patients had medically uncontrolled glaucoma as indicated by high intraocular pressure (IOP), worsening visual field, or optic nerve head changes in whom primary trabeculectomy was indicated. Patients were older than 18 years with medically uncontrolled glaucoma and no history of incisional glaucoma surgery. Patients were randomized to MMC delivered by preoperative subconjunctival injection or by intraoperative direct scleral application using surgical sponges during trabeculectomy. Comprehensive eye examinations were conducted at 1 day, 1 week, 6 weeks, 3 months, and 6 months postoperatively. Subconjunctival 5-fluorouracil injections were given postoperatively, as needed. The primary outcome was the proportion of patients who demonstrated IOP of <21 mm Hg and ≥30% reduction in IOP from baseline. Secondary outcome measures included the number of IOP-lowering medications, bleb morphology using the Indiana Bleb Appearance Grading Scale, and complication rates. RESULTS: Participants (n = 100) were randomized into groups matched for baseline demographics, glaucoma status, and baseline IOP. At 6 months, there were no significant differences between the injection (n = 38) and sponge (n = 40) groups in surgical success (P = .357), mean IOP (P = .707), number of glaucoma medications (P = 1.000), bleb height (P = .625), bleb extension (P = .216), bleb vascularity (P = .672), or complications rates. CONCLUSION: Both techniques of MMC delivery (subconjunctival injection and direct scleral application) resulted in comparable surgical outcomes and bleb morphologies.

Successful Treatment of Necrotizing Retinitis with Epstein-Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection.

PURPOSE: To present a case of necrotizing retinitis with Epstein-Barr virus (EBV)-positive ocular fluid in a patient with sudden unilateral vision loss, which was successfully treated with intravitreal methotrexate (MTX) injections. METHODS: Retrospective case report. RESULTS: An 83-year-old female who had been on methylprednisolone for 20 years due to interstitial pneumonia developed vitreous opacity and extensive necrotizing retinitis with retinal hemorrhage sparing the posterior pole in the left eye. Multiplex polymerase chain reaction (PCR) for viral DNA using vitreous sample was positive for EBV but negative for herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Real-time PCR detected EBV-DNA in aqueous humor but not in peripheral blood sample. Serologic testing was negative for Toxoplasma gondii, syphilis, and HIV. The patient did not respond to systemic ganciclovir or acyclovir. Subsequent treatment with intravitreal MTX resulted in immediate clinical improvement correlating with a decrease in copy number of EBV-DNA. CONCLUSION: Intravitreal MTX may be an effective treatment option for patients with necrotizing retinitis and EBV-positive ocular fluid not responding to conventional antiviral therapy.

Effectiveness of trabeculectomy with mitomycin C for glaucomatous eyes with low intraocular pressure on treatment eye drops.

PURPOSE: To examine the efficacy and safety of current trabeculectomy with mitomycin C in Japan for glaucomatous eyes with low intraocular pressure (IOP). METHODS: Two hundred ninety-four eyes of 294 patients with IOP ≤21 mmHg before surgery were studied; all patients were participants in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS), a multicentre, prospective, cohort study conducted at 34 ophthalmological institutions throughout Japan. All eyes had an intraocular pressure ≤ 21 mmHg and had undergone trabeculectomy alone or phacotrabeculectomy. Two success criteria were used: Criterion A comprised 20% reduction of baseline IOP and Criterion B comprised 30% reduction of baseline IOP. The primary outcome was the success rate for each of these criteria. RESULTS: The qualified success rates were 87.3% for Criterion A and 42.0% for Criterion B at 5 years. Mean IOP was significantly reduced, from 16.7 ± 2.7 to 11.6 ± 4.0 mmHg at 5 years after trabeculectomy (p < 0.0001); the number of anti-glaucoma medications significantly decreased from 2.7 ± 1.1 to 1.0 ± 1.2 (p < 0.0001) at 5 years after the surgery. Three or more trabeculectomies, and needling were related to increased risk of failure. Incidences of postoperative hyphema, infection, shallow anterior chamber and bleb leakage were 2.4%, 2.4%, 2.0% and 3.4%, respectively. CONCLUSIONS: This study showed that trabeculectomy with mitomycin C is an effective procedure with few surgical complications for reducing IOP in patients, even if preoperative IOP was within the normal range.

Fifteen-year results of a randomized controlled trial comparing 0.02% mitomycin C, limbal conjunctival autograft, and combined mitomycin C with limbal conjunctival autograft in recurrent pterygium surgery.

PURPOSE: To compare the long-term outcomes of recurrent pterygium surgery between three different techniques. METHODS: We performed a 15-year follow-up study of a randomized controlled study on surgical management of recurrent pterygium. Group 1 received limbal conjunctival autograft (LCAU); group 2 received intraoperative mitomycin C (MMC) 0.02% for 5 min; and group 3 received combined LCAU + MMC 0.02% for 5 min. Consecutive patients enrolled in the original study (from April 2001 to March 2003) were invited back for a detailed clinical examination to document the long-term outcomes. The main outcome measures included the recurrence rate, residual conjunctival bed status, and complications from any of the surgical methods. RESULTS: Sixty-two patients were recruited in the original study. Eight patients had passed away and 12 patients were uncontactable or not responded. One patient who had bilateral operations refused to return for follow-up and one eye had insufficient data for analysis. Finally, 40 eyes of 40 patients were included for analyses. One eye developed a recurrence over 15 years and none required a tertiary pterygium operation. The patient received LCAU for a temporal recurrent pterygium developed a 2.2-mm recurrence. CONCLUSIONS: All three techniques yielded favorable outcomes for patients with recurrent pterygium. The use of LCAU was associated with better cosmetic outcome.

Change in visual acuity 12 and 24 months after transscleral ab interno glaucoma gel stent implantation with adjunctive Mitomycin C.

PURPOSE: To analyze changes in best-corrected visual acuity (BCVA) after implantation of the transscleral ab interno glaucoma gel stent (XEN Gel Stent; Allergan, Dublin) in patients with open-angle glaucoma. METHODS: In a single-center, prospective, non-randomized study of 137 eyes with open-angle glaucoma which underwent implantation with XEN, 69 eyes underwent XEN implantation alone (group 1) and 68 eyes underwent XEN implantation and cataract surgery (group 2). BCVA (Bailey-Lovie chart, logMAR scale) was evaluated at baseline, postoperative day 1, weeks 1 and 2, and months 1, 3, 6, 12, and 24. Risk factors for decline in BCVA were analyzed in multivariate models. RESULTS: Baseline BCVA in group 1 was 0.21 ± 031; the group's mean BCVA did not change at any postoperative visit, although a ≥ 2-line loss of BCVA was detected in 15% (95% CI 7-29%) and 4% (95% CI 0-20%) after months 12 and 24, respectively. Baseline BCVA in group 2 was 0.33 ± 031; vision increased significantly at months 3 (0.22 ± 0.29, p = 0.015), 6 (0.20 ± 0.26, p = 0.006), 12 (0.18 ± 0.29, p = 0.001), and 24 (0.18 ± 0.29, p = 0.005). A ≥ 2-line loss of BCVA was reported in 4% (95% CI 1-15%) and 7% (95% CI 1-24%) after months 12 and 24, respectively. CONCLUSIONS: There was no deterioration of BCVA in group 1; those in group 2 had an overall significant increase in BCVA. BCVA decrease was lower than is typically reported in the literature post-trabeculectomy.

The efficiency of low-dose hepatitis B immunoglobulin plus nucleos(t)ide analogs in preventing posttransplant hepatitis B virus recurrence

Background/aim: In this study, the efficiency of using low-dose hepatitis B immunoglobulin (HBIG) plus antiviral treatment according to individual needs has been evaluated in posttransplant hepatitis B virus (HBV) patients. Materials and methods: We retrospectively evaluated 179 patients who were admitted between 2009 and 2014. Five thousand IU intravenous HBIG was given in the anhepatic phase, and 400 IU/day intramuscular (IM) HBIG was given in the posttransplant period. After HBsAg seroconversion, 400 IU IM HBIG was continued as prophylaxis every two weeks. Results: The average follow-up period was 26 (2­65) months. Seventy patients had hepatocellular carcinoma (HCC). The HBV recurrence was 4.5% in the first year, and 5.8% in the third year. The HBsAg became negative in 11 (2­63) days, and anti-HBs became positive in 9 (1­31) days. HBsAg positivity occurred in 6 patients during the follow-up period. Five of these patients were those who underwent transplantation due to HCC. In 5 of the HCC patients, in whom HBsAg became positive, tumor recurrence was observed after 0.3­9.9 months. HBsAg positivity was more frequently detected in patients with HCC (P = 0.009). Conclusion: The HBV recurrence should be evaluated as a predictor of the HCC recurrence in patients who were transplanted due to HCC.

Midterm outcome of mitomycin C augmented trabeculectomy in open angle glaucoma versus angle closure glaucoma.

Purpose: The purpose of this study is to evaluate the efficacy and safety of Trabeculectomy with Mitomycin C in Open angle glaucoma versus Angle closure glaucoma. Methods: The medical records of patients who underwent Trabeculectomy with Mitomycin C were reviewed and followed for three years, divided into two groups: group 1: Open Angle Glaucoma (n = 41) and group 2: Angle Closure Glaucoma (n = 67). Success criterion was measured as Intraocular Pressure ≤21 mmHg with (qualified) or without (complete) use of Antiglaucoma medications. Results: A total number of 108 eyes of 137 patients were undertaken. Mean preoperative Intraocular pressure in group 1 was 31.4 ± 10.5 mmHg and in group 2 was 33.1 ± 9.4, which reduced to 10.5 ± 3.4, 10.5 ± 2.6, 11.6 ± 3.6, 11.0 ± 2.7, 11.0 ± 2.7 in group 1 and 10.9 ± 2.8, 12.0 ± 3.8, 12.8 ± 4.9, 12.4 ± 3.9, 12.4 ± 3.7 in group 2 with P value = 0.566, 0.032, 0.168, 0.049, 0.049 at three, six months, one, two, three years, respectively, with P < 0.001 at each visit. The number of Antiglaucoma medications was reduced from 0.75 ± 0.89 to 0.43 ± 0.55 at 3 yrs (P = 0.002). At 36 months follow-up, overall, 50.0% and 48.2% of eyes achieved complete and qualified success, respectively. Sub-group analysis showed that the success rate was higher in group 1 (68.3%) compared to group 2 (55.2%). Overall, complications such as hypotony (1.8%), choroidal detachment (2.8%), encapsulated bleb (2.8%), and bleb leakage (1.8%) were encountered. Conclusion: Primary Trabeculectomy with Mitomycin C is a safe and effective means of controlling Intraocular Pressure in both groups with good success and low rates of sight-threatening complications.

The optimization of methadone dosing whilst treating with rifampicin: A pharmacokinetic modeling study.

BACKGROUND: The use of oral methadone in opioid substitution treatment (OST) for the management of opioid use disorder is established clinical practice. Confounding treatment is the increased risks of contracting Mycobacterium tuberculosis, the mainstay treatment of which incorporates the potent CYP 2B6 inducer rifampicin. METHODS: This study applied pharmacokinetic modelling using virtual clinical trials, to pharmacokinetically quantify the extent and impact of rifampicin-mediated drug-drug interactions (DDI) on methadone plasma concentrations. An R-methadone model was developed and validated against 11 retrospective clinical studies prior to use in all subsequent studies. The aims were to investigate: (i) the impact of the DDI on daily methadone doses of 60 mg, 90 mg and 120 mg; (ii) dose escalation during rifampicin and (iii) dose reduction following rifampicin cessation. RESULTS: A dose increase to 160 mg daily during rifampicin treatment phases was required to maintain peak methadone plasma concentrations within a derived therapeutic window of 80-700 ng/mL. Dose escalation prior to rifampicin initiation was not required and resulted in an increase in subjects with supra-therapeutic concentrations. However, during rifampicin cessation, a dose reduction of 10 mg every 2 days commencing prior to rifampicin cessation, ensured that most patients possessed a peak methadone plasma concentration within an optimal therapeutic window. IMPLICATIONS: Rifampicin significantly alters methadone plasma concentrations and necessitates dose adjustments. Daily doses of almost double those used perhaps more commonly in clinical practice are required for optimal plasma concentration and careful consideration of dose reduction strategies would be required during the deinduction phase.

Comparison of 2-year-results of mitomycin C-augmented trabeculectomy with or without cataract extraction in glaucoma patients.

PURPOSE: Comparison of the 2-year results of phacotrabeculectomy (CET) and trabeculectomy (TE), both augmented with mitomycin C. METHODS: This prospective study enclosed 246 eyes in 246 consecutive patients that had undergone trabeculectomy (n = 85) or phacotrabeculectomy (n = 161, hereof n = 10 phacoretrabeculectomy) augmented by mitomycin C. Endpoints were best corrected visual acuity (BCVA), intraocular pressure (IOP), and number of antiglaucomatous medications at baseline, 3 months, and 2 years postoperatively. Postoperative management involved local steroid application and laser suture lysis according to a standardized protocol. RESULTS: Both interventions reduced IOP statistically significant and stable. In the phacotrabeculectomy group BCVA improved from 0.45 ± 0.47 logMAR units preoperatively to 0.28 ± 0.54 logMAR units at 2 years (p < 0.001) and remained unchanged in the trabeculectomy group. After 2 years IOP reduced from 22.5 ± 7.2 mm Hg preoperatively to 11.5 ± 3.1 mm Hg in the TE group and from 20.0 ± 5.4 mm Hg to 12.5 ± 4.8 mm Hg in the CET group (both p > 0.05). The mean number of antiglaucomatous medications was significantly reduced from 2 ± 1 in both groups to 0.3 in the trabeculectomy group and to 0.4 in the phacotrabeculectomy group. With this standardized surgical procedure and postoperative protocol, there was no need for local postoperative antimetabolites. No Tenon's capsule cysts developed. In the subgroup of patients with phacoretrabeculectomy BCVA and IOP improvements were comparable to the phacotrabeculectomy group outcomes. CONCLUSIONS: Phacotrabeculectomy is comparably as effective as trabeculectomy alone in reducing IOP and the need for antiglaucomatous medication over a time interval of 2 years. We found indications that this favourable therapeutic effect is also true for patients needing phacoretrabeculectomy treatment.

Intraocular application of Mitomycin C to prevent proliferative vitreoretinopathy in perforating and severe intraocular foreign body injuries.

AIM: To assess the long-term anatomical and functional outcomes in addition to complications of a new surgical technique of localized intraocular application of mitomycin C (MMC) to prevent proliferative vitreoretinopathy (PVR) in eyes with open globe trauma. METHODS: Prospective non-comparative interventional case series of 16 consecutive eyes with perforating and deep choroidal impact foreign body injuries presenting over a 2-year period. Patients underwent vitrectomy with intraocular application of MMC at the site of the chorioretinal injury and were followed-up for 1 year. The primary outcome measure was the rate of postoperative PVR. Secondary outcome measures were number of vitreoretinal surgeries (VRS) required, best corrected visual acuity (BCVA), final anatomical success rate and globe survival rate (GSR). RESULTS: Patients underwent VRS at a mean time of 8.5 ± 4.6 days after the injury. Postoperative PVR developed in 2 (13 %) eyes and required only one additional VRS each. One other eye underwent further peeling of an epimacular membrane. BCVA improved from mean LogMAR 3.08 ± 0.72 preoperatively to 0.66 ± 0.79 at 1 year. All 10 eyes without a macular injury had a final BCVA of LogMAR 0.40 or better. The final anatomical success rate was 94% and GSR rate was 100%. There were no complications related to the intraocular use of MMC. CONCLUSIONS: Vitrectomy and intraocular application of Mitomycin C may have a potential role in reducing the rate of post traumatic PVR and improving anatomical and functional outcomes in eyes with perforating and deep choroidal impact foreign body injuries.

Evaluation of antimitotic and antiangiogenic effect of preoperative subconjunctival application of mitomycin C in primary pterygium: a randomized trial.

PURPOSE: To evaluate the influence of preoperative mitomycin C (MMC) on the proliferative behavior of fibroblasts and fibrovascular tissue derived from the primary pterygium using the immunohistochemical method (Ki67 and CD34). DESIGN: Randomized clinical trial. SUBJECTS, PARTICIPANTS AND/OR CONTROLS: Sixty-five patients with primary pterygium were randomly selected and divided into one of three groups. The control group had 29 patients that were only submitted to pterygium removal. The group that received the MMC injection a month before surgery had 16 patients, and the group that received the MMC 2 weeks before surgery had 20 patients. Each patient only had one eye operated on. METHODS: Sixty-five patients were selected to undergo pterygium excision surgery. We randomly placed the patients into three groups: one without MMC (n = 29), one with MMC application 1 month before surgery (n = 16) and another with MMC application 2 weeks before surgery (n = 20). Subconjunctival injection was applied with 0.1 ml of 0.02% MMC in the pterygium body, and patients were followed for 2 years. MAIN OUTCOME MEASURES: Proliferative behavior of fibroblasts and fibrovascular tissue using the immunohistochemical method (Ki67 and CD34) comparing the three groups. RESULTS: Of the total 29 patients (44.6%) in the control group (without MMC application), 11 cases had recurrence (37.9%), of which seven (63.6%) were within 3 months of follow-up and four (36.3%) within 6 months of follow-up. The mean proliferation index of the recurrent cases was 4.5%, and of the cases without recurrence, it was 6.1%. There were 16 patients (24.6%) in the MMC application group 1 month before surgery, in which one case (6.25%) recurred at 6 months. In the group with MMC application 2 weeks before surgery, of the total of 20 patients (30.7%), there was one case of recurrence (5%) at 6 months. The proliferation index of the group that had MMC administered and did not have a recurrence was 7.2%, and in the group with recurrence, it was 6.4%. The CD34-labeled cell count was 5.8% among cases with recurrence and 5.6% in cases without recurrence. No side effects of MMC application were reported during the study follow-up period. CONCLUSION: MMC was efficient to reduce the recurrence index despite the absence of a direct relation with its antimitotic and antiangiogenic effect in the samples that were analyzed.

Safety and complications after three different surface ablation techniques with mitomycin C: a retrospective analysis of 2757 eyes.

BACKGROUND: To evaluate the safety and spectrum of complications of three excimer laser surface ablation techniques (SATs) with an intraoperative application of mitomycin C (MMC) 0.02%. A retrospective, non-comparative large case series. METHODS: SATs were performed on 2757 eyes with a preoperative spherical equivalent (SE) of - 4.41 ± 2.44 and a Wavelight Allegretto 200 platform. Ablation zone diameters between 6.0 and 7.0 mm were used according to mesopic pupil size. All patients were treated with an intraoperative application of MMC for 30 to 90 s depending on refractive error. The mean follow-up time was > 3 months (107 ± 24 days). Complication range and incidence were analyzed retrospectively and safety index was calculated. RESULTS: Two thousand seven hundred and fifty-seven eyes met the inclusion criteria for surface ablation. Two thousand five hundred and seventy-three eyes were assigned to alcohol-assisted photorefractive keratectomy (APRK), 135 eyes to transepithelial photorefractive keratectomy (TPRK), and 49 eyes to off-flap epithelial laser in situ keratomileusis (EpiLASIK/EpiK). Overall, the safety index was 1.06 ± 0.28. Haze was graded according to the Fantes scale. Haze incidence rates were highest in the TPRK group (14.81%) and comparably low in APRK (2.95%) and EpiK (4.08%) groups. CONCLUSIONS: Intraoperative topical application of MMC (0.02%) results in good safety and no severe side effects. However, highest incidence of haze was observed after TPRK. The more frequent peripheral localization of haze might be attributed to large ablation zones and the wavefront optimized ablation profile especially in the PTK modus of the laser platform.

Combination Therapy With Neuraminidase and Polymerase Inhibitors in Nude Mice Infected With Influenza Virus.

Background: Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Methods: Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof. Results: Combination therapy for 28 days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Conclusions: Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.

Development of a Prodrug of Levofloxacin to Avoid Chelation with Al3+ and of Pemetrexed Dimedoxomil Esters for Oral Administration.

An ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) avoids insoluble chelate formation with metal-containing drugs in the intestinal tract and is rapidly hydrolyzed to the parent drug. Furthermore, the minimum inhibitory concentration confirms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria flora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after modification of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with trifluoroacetic acid (TFA) in CH2Cl2 at a temperature of 0°C for 2 h. A serum pemetrexed concentration of >2 µg/mL was observed after oral administration of pemetrexed dimedoxomil at a dose of 60 mg/kg to rats.

Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives.

Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; however, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral suppression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resistance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facilitate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous "dual" strategy, sequential combination "add-on" strategy, and "switch" strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with interferon monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treatment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated.

SPATHOLOBUS SUBERECTUS STEM EXTRACT IMPROVES THE PROTECTIVE EFFECT OF HEPARIN ON CERULEIN-INDUCED PANCREATITIS.

BACKGROUND: The present study evaluates the effect of Spatholobus suberectus stem extract (SS) in the management of pancreatitis alone and in combination with heparin. MATERIAL AND METHODS: Pancreatitis was induced pancreatitis by cerulean (50µg/kg, i.p.) five times at an interval of 1 h without any pretreatment of drug. Rats were treated with SS (100 and 200 mg/kg, p. o.) and heparin (150 U/kg, i.p.) alone and in combination for the duration of a week. Later pancreatic weight and blood flow was estimated and different biochemical parameters like concentration of D-dimer and Interleukin 1ß (IL-Ιß) and activity of amylase and lipase were determined in blood of pancreatitis rats. Moreover effect of drug treatment on DNA synthesis and histopathology was also estimated on cerulean induced pancreatitis rats. RESULT: Results of this study suggest that treatment with SS alone and in combination with heparin significantly increase in prothrombin time and pancreatic blood flow than negative control group. There was significant decrease in concentration of IL-Ιß and D-dimer and activity of amylase and lipase in SS and heparin treated group than negative control group. Pancreatic DNA synthesis was also found to be reduced in SS and heparin alone and in combination treated group. Histopathology study also reveals that treatment with SS and heparin alone and in combination reduces edema, hemorrhages, leukocyte infiltration in the TS of pancreatic tissues. CONCLUSION: Present study concludes that treatment with SS alone effectively manages the pancreatitis by ceasing the inflammatory pathway and potentiates the effect of heparin in the management of pancreatitis.