Antagonizing pathological α-synuclein-mediated neurodegeneration by J24335 via the activation of immunoproteasome.

The aggregation of misfolded proteins, such as α-synuclein in Parkinson's disease (PD), occurs intracellularly or extracellularly in the majority of neurodegenerative diseases. The immunoproteasome has more potent chymotrypsin-like activity than normal proteasome. Thus, degradation of α-synuclein aggregation via immunoproteasome is an attractive approach for PD drug development. Herein, we aimed to determine if novel compound, 11-Hydroxy-1-(8-methoxy-5-(trifluoromethyl)quinolin-2-yl)undecan-1-one oxime (named as J24335), is a promising candidate for disease-modifying therapy to prevent the pathological progression of neurodegenerative diseases, such as PD. The effects of J24335 on inducible PC12/A53T-α-syn cell viability and cytotoxicity were evaluated by MTT assay and LDH assay, respectively. Evaluation of various proteasome activities was done by measuring the luminescence of enzymatic activity after the addition of different amounts of aminoluciferin. Immunoblotting and real-time PCR were employed to detect the expression of various proteins and genes, respectively. We also used a transgenic mouse model for behavioral testing and immunochemical analysis, to assess the neuroprotective effects of J24335. J24335 inhibited wild-type and mutant α-synuclein aggregation without affecting the growth or death of neuronal cells. The inhibition of α-synuclein aggregation by J24335 was caused by activation of immunoproteasome, as mediated by upregulation of LMP7, and increased cellular chymotrypsin-like activity in 20S proteasome. J24335-enhanced immunoproteasome activity was mediated by PKA/Akt/mTOR pathway activation. Moreover, animal studies revealed that J24335 treatment markedly mitigated both the loss of tyrosine hydroxylase-positive (TH-) neurons and impaired motor skill development. This is the first report to use J24335 as an immunoproteasome enhancing agent to antagonize pathological α-synuclein-mediated neurodegeneration.

The Effect of Trypsin-Chymotrypsin on Postoperative Pain after Single Visit Endodontic Treatment: A Randomized Controlled Trial.

INTRODUCTION: The efficacy of trypsin-chymotrypsin in postoperative pain management following single-visit root canal treatment of teeth with symptomatic irreversible pulpitis was evaluated. Additionally, synergistic effects with nonsteroidal anti-inflammatory drugs and reported side effects were also investigated. METHODS: This prospective, parallel, triple-blinded phase IV randomized controlled trial included 60 patients with mandibular first molars exhibiting symptomatic irreversible pulpitis. The patients were randomly allocated using computer software to one of four treatment groups (n = 15 each), and either ibuprofen (600 mg), ambezim-G (trypsin 5mg-chymotrypsin 5 mg), a combination of both, or a placebo drug were administered postoperatively. The participants scored pain intensity at different time-intervals using a numerical scale, and passive surveillance of harm was used to detect clinical safety. Age was compared between groups using a one-way analysis of variance test. Pain scores were analyzed using the Kruskal-Wallis and Friedman's tests and, if significant, Dunn's test was used for pairwise comparisons. The chi-square test was used to compare qualitative data, and the significance level was set at P value ≤ .05. RESULTS: All interventions were found to be effective in reducing postoperative pain, and no statistically significant differences were observed between the ibuprofen, trypsin-chymotrypsin, and combination groups. However, all 3 groups differed significantly from the placebo group. The safety profile of the interventions did not differ significantly. CONCLUSIONS: Trypsin-chymotrypsin exhibits comparable efficacy to nonsteroidal anti-inflammatory drugs. No synergistic effects occur when the 2 are used in combination. This is the first randomized controlled trial to assess the effects of proteolytic enzymes on postendodontic pain. TRIAL REGISTRATION: clinicaltrials.gov, Identifier: NCT05479747.

Study of the gastrointestinal bioavailability of a pancreatic extract product (Zenpep) in chronic pancreatitis patients with exocrine pancreatic insufficiency.

INTRODUCTION: The Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine. METHODS: In this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [14C]-PEG instillation by an attached Dobhoff tube in the duodenal bulb). Patients received Ensure Plus® alone and Ensure Plus with Zenpep (75,000 USP lipase units) in random order. The bioavailability of Zenpep was estimated by comparing the recovery of lipase, amylase, chymotrypsin activity in two treatment conditions. 14C-PEG was used to correct duodenal aspirates volume. The primary efficacy endpoint was lipase delivery in the duodenum after Zenpep administration under fed conditions. Secondary efficacy endpoints included chymotrypsin and amylase delivery, serum CCK levels, and measuring duodenal and gastric pH. RESULTS: Zenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [14C]-PEG was 61%. Zenpep was generally well tolerated. All adverse events were mild and transient. CONCLUSIONS: In CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.

Negative Pressure Wound Therapy With Chymotrypsin Irrigation: A Maximal Implant Retention Procedure Treating the Exposure/Infection of Titanium Mesh in Cranioplasty.

This preliminary study aims to investigate the effects of a maximal implant retention procedure. The authors retrospectively reviewed the use of negative pressure wound therapy with chymotrypsin irrigation treating implant infection/exposure in titanium mesh cranioplasty by comparing patients with titanium mesh totally retained, partially removed, or totally removed according to the evaluation during the surgery. Negative pressure wound therapy with chymotrypsin irrigation was applied 5 days after the surgery. The negative pressure was set at -125 to -150 mmHg. A total of 21 patients were included, 4 patients treated with titanium mesh totally removed; 3 patients treated with titanium mesh partially removed; and 14 patients treated with U-shape debridement with titanium mesh preserved completely. However, 1 patient in the U-shape group required a second debridement to remove all implant. Negative pressure wound therapy with chymotrypsin irrigation is a novel procedure and could be used to treat implant-related infection without the exchange of implant.

[Clinical application of vacuum sealing drainage combined with chymotrypsin in the treatment of post-traumatic mandibular osteomyelitis].

This article introduces the combined application of vacuum sealing drainage (VSD) and chymotrypsin in the treatment of post-operative mandibular osteomyelitis. The lesion was washed by chymotrypsin (4000U) and saline (500 ml). VSD is effective in the treatment of traumatic mandibular osteomyelitis. This study investigates the effect of VSD combined with chymotrypsin in the treatment of patients with osteomyelitis after mandibular trauma. It is proved that it has a good effect in ensuring drainage, controlling infection and retaining internal fixation, and can create a good environment for fracture healing.

The Role of Trypsin:Chymotrypsin in Tissue Repair.

Tissue damage of all types, such as surgical or accidental injuries, fractures, and burns, stimulates a well-orchestrated, physiological process of healing, which ultimately leads to structural and functional restoration of the damaged tissues. The tissue repair process can be broadly divided into four continuous and overlapping phases-hemostasis and coagulation, inflammation, proliferation, and remodeling. If the process is interrupted or halted during any stage, it leads to impaired healing and formation of a chronic wound. Chronic wounds are associated with significant morbidity, mortality, and poor quality of life. Therefore, prompt and effective management of acute tissue injury is necessary to prevent it from progressing to a chronic wound. Proteolytic enzymes have been used to facilitate tissue repair since ancient times. Trypsin:chymotrypsin is an oral proteolytic enzyme preparation which has been in clinical use since the 1960s. It provides better resolution of inflammatory symptoms and promotes speedier recovery of acute tissue injury than several of the other existing enzyme preparations. This review article revisits the role and clinical utility of trypsin:chymotrypsin combination in tissue repair. FUNDING: Torrent Pharmaceuticals Limited.

Chymotrypsin with sialendoscopy-assisted surgery for the treatment of chronic obstructive parotitis.

Chronic obstructive parotitis (COP) is a common disease of the parotid gland. A total of 104 patients with COP were identified and randomized into a treatment group (52 cases) and a control group (52 cases). All patients underwent sialography and salivary gland scintigraphy (SGS) examinations before surgery. The patients in the treatment group received chymotrypsin combined with gentamicin via interventional sialendoscopy to irrigate the duct, and the control group received gentamicin alone. All patients were asked to record their pain on a visual analogue scale (VAS) before treatment and at 1 week, 2 weeks, 1 month, 3 months, and 6 months after surgery. The VAS score for pain intensity was decreased at 1 week post-treatment in both groups (P<0.05). Compared to the control group, the VAS score was lower in the treatment group at 1 week, 2 weeks, and 1 month post-treatment (P<0.05). The 6-month postoperative SGS results showed improved uptake and excretion in both groups (P<0.05). The treatment group exhibited higher scores for postoperative SGS excretion than the control group (P<0.05). The administration of chymotrypsin combined with gentamicin by sialendoscopy is effective for the treatment of non-stone-related COP and specifically improves the excretion function of the parotid gland.

A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management.

INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain. METHOD: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

α-Chymotrypsin regulates free fatty acids and UCHL-1 to ameliorate N-methyl nitrosourea induced mammary gland carcinoma in albino wistar rats.

This study was undertaken to investigate the effect of α-chymotrypsin on methyl nitrosourea (MNU) induced mammary gland carcinoma in albino wistar rats. Animals were randomized into four groups (six animals in each). Group I (sham control 0.9 % normal saline p.o.); Group II (toxic control, MNU 47 mg/kg, i.v.); Group III (α-chymotrypsin, 5 mg/kg, p.o.); Group IV (α-chymotrypsin, 10 mg/kg p.o.). Toxicity was induced by single i.v. injection of MNU followed by α-chymotrypsin supplementation therapy for 100 days. MNU treatment was evident with increased alveolar bud count, differentiation score, upregulated inflammatory enzymes markers (COX, LOX and NO) antioxidative stress markers (TBARs, SOD, catalase and GSH).MNU associated toxicity was also ascertained by PGP 9.5 and NF-κB expression in the mammary gland tissue followed by FAME analysis for fatty acid profiling. α-chymotrypsin afforded significant protection against the deleterious effects of MNU.

Sperm with an abnormal hypo-osmotic swelling test--normal fertilization, normal embryo development, but implantation failure.

PURPOSE: To review the clinical importance of including the hypo-osmotic swelling (HOS) test in routine male fertility testing which in general is not evaluated by most physicians dealing with infertility. MATERIALS AND METHODS: Pregnancy rates were evaluated in patients with low HOS test scores. A low HOS test was specifically defined as having less than 50% of sperm exhibiting the normal physiologic response of tail swelling, when subjected to a hypo-osmolar solution. Pregnancy rates of patients with low HOS test were examined after intercourse, intrauterine insemination (IUI), conventional oocyte insemination, and in vitro fertilization (IVF). Patients with a low HOS test were also treated with a protein digestive enzyme chymotrypsin. Patients receiving intervention then underwent IUI, IVF with conventional oocyte insemination, or IVF with intracytoplasmic sperm injection (ICSI). Pregnancy rates of the cohort receiving intervention were then examined for comparison. RESULTS: The HOS test abnormality leads to normal fertilization but almost invariably negatively effects embryo implantation. Treatment with chymotrypsin, or performing IVF with ICSI, can overcome the toxic protein causing the embryo implantation defect. This toxic protein may be cryolabile and freezing sperm or embryos may prove to be another mode of therapy. CONCLUSIONS: The HOS abnormality may be the most reliable semen abnormality predicting failure to conceive even with IVF unless the defect is negated. Therapy is very effective. Unfortunately this test is rarely evaluated by most infertility specialists but it should be. The frequency increases with age.

Degradation of MSCRAMM target macromolecules in VLU slough by Lucilia sericata chymotrypsin 1 (ISP) persists in the presence of tissue gelatinase activity.

Venous leg ulcer slough is unpleasant to the patient and difficult to manage clinically. It harbours infection, also preventing wound management materials and dressings from supporting the underlying viable tissues. In other words, slough has significant nuisance value in the tissue viability clinic. In this study, we have sought to increase our knowledge of slough by building upon a previous but limited analysis of this necrotic tissue. In particular, slough has been probed using Western blotting for the presence of proteins with the capacity to engage microbial surface components recognising adhesive matrix macromolecules. Although the samples were difficult to resolve, we detected fibrinogen, fibronectin, IgG, collagen, human serum albumin and matrix metalloproteinase-9. Furthermore, the effect of a maggot-derived debridement enzyme, chymotrypsin 1 on macromolecules in slough was confirmed across seven patient samples. The effect of chymotrypsin 1 on slough confirms our thesis that this potential debridement enzyme could be effective in removing slough along with its associated bacteria, given its observed resistance to intrinsic gelatinase activity. In summary, we believe that the data provide scientists and clinicians with further insights into the potential molecular interactions between bacteria, wound tissue and Lucilia sericata in a clinically problematic yet scientifically interesting wound ecosystem.

Alpha-chymotrypcin ameliorates neuroinflammation and apoptosis characterizing Alzheimer's disease-induced in ovarictomized rats.

OBJECTIVE: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Very little is known about the causes of AD, except that its end stages involve extensive neuronal loss and the appearance of distinctive neuropathological features. This study was under taken to investigate the role of α-chymotrypcin (α-ch) in management of AD-induced in ovariectomized rats. DESIGN: Sixty female Sprague Dawley rats were divided into four groups n=15, (1) normal control group (con), (2) group underwent surgery to remove ovaries (ovx control group), (3) ovx group received aluminum chloride in a dose of 17 mg/kg daily for 2 months to induce AD (AD group), (4) AD group treated with α-chymotrypcin (α-ch) at dose (8.1 unit/rat/day) which is equivalent to the recommended human dose (α-ch-treated group) for three months. At the end of the experimental period, rats were sacrificed; brain samples were obtained for different biochemical analyses and histopathological examination. The biochemical analyses included determination of tumor necrosis factor-α (TNF- α), IL-18, monocyte chemo attractant protein-1 MCP-1, FAS, B-cell lymphoma 2 (Bcl2). RESULTS: In comparison with normal control group, the ovx control group recorded significant increase in the brain levels of TNF-α, IL-18, MCP-1 and FAS. On the other hand, the brain level of Bcl2 was significantly decreased. Also, AD group showed a significant increase in TNF-α, IL-18, MCP-1 and FAS levels in brain tissue. In contrast, significant decrease in brain Bcl2 level was detected in AD group as compared to the ovx control group. However, the treatment of AD group with α-chymotrypcin caused an improvement in the most studied biochemical parameters as indicated by decreased brain levels of TNF-α, IL-18, MCP-1 and FAS accompanied with significant increase in the level of Bcl2 compared to AD group. Histopathological investigation of brain tissue of ovx rats administered with aluminum (AD group) showed AD plaques. While, AD group treated with α-chymotrypcin showed great improvement in the brain morphological structure with the disappearance of amyloid plaques. CONCLUSION: This study revealed that α-chymotrypcin significantly ameliorates the neuroinflammation characterizing Alzheimer's disease in ovariectomized rats due to it's proteolytic activity as well as it's anti-inflammatory effect.

Recombinant Lucilia sericata chymotrypsin in a topical hydrogel formulation degrades human wound eschar ex vivo.

Larval biotherapy is a debridement tool used in wound management. The mechanism of action involves degradation of eschar by serine proteases including chymotrypsin within the alimentary fluids of first instar Lucilia sericata. With the rationale of obviating some limitations of biotherapy, including cost, complexity of use, and patient reticence, the present study describes a mobile hydrogel formulation containing freeze-dried recombinant L. sericata chymotrypsin designed for topical application. Neither freeze-drying nor formulation into the hydrogel significantly attenuated the measured activity of released enzyme compared to fresh-frozen enzyme in aqueous solution. Gel electrophoresis confirmed qualitatively that the chymotrypsin/hydrogel formulation both with and without supplementary urea at 10% (w) /(v) degraded human chronic wound eschar ex vivo. Mindful that the hallmark of intractability of chronic wounds is aberrant biochemistry, the pH activity profile for the enzyme/hydrogel formulation was compared with exudate pH in chronic wounds of mixed aetiology in a cohort of 48 hospital in-patients. Five patients' wounds were acidic, however, the remainder were predominantly alkaline and coincided with the pH optimum for the insect enzyme. Thus, a recombinant L. sericata chymotrypsin and hydrogel formulation could represent a pragmatic alternative to larval therapy for the management of chronic wounds.

Cheilitis granulomatosa.

Cheilitis granulomatosa is a rare disease characterised by the recurrent labial swelling of one or both lips with the possibility of the condition to remain on a permanent basis. The disease may appear independently or it may be linked to a paralysis such as the facial and lingua plicata which then characteristic of the Melcersson-Rosenthal Syndrome. The aim of this paper is to show a case of a patient with the granulomatosae cheilitis and lingua plicata whose reaction to the Chymoral Forte treatment was excellent.

Changes on venous diameter and leg perimeter with different clinical treatments for moderate chronic venous disease: evaluation using Duplex scanning and perimeter measurements.

AIM: To evaluate changes on venous diameter and perimeter of lower limbs in chronic venous disorder (CVD) patients after different clinical treatments for four weeks. METHODS: Fifty-two female patients classified as C2,s or C2,3,s (CEAP classification) were allocated consecutively in three groups: Cirkan (40 mg of the root extract of Ruscus aculeatus + 100 mg of flavonoid hesperidine methylchalcone + 200 mg of vitamin C per pill); elastic compression stockings (ECS) and no treatment (NT). Diameters were determined by duplex ultrasound and perimeter with Leg-O-Meter. RESULTS: After treatment, Cirkan significantly decreased popliteal vein and great saphenous vein (GSV) diameters bilaterally and ECS decreased popliteal vein diameter bilaterally and GSV and varices only on the left limb. Perimeters changed only with ECS. Clinical scores changed between Cirkan x NT and ECS x Cirkan. Disability score varied for ECS x NT and Cirkan x NT. chi2 test detected different distribution frequency for C3 and C2 classes according to treatment: ECS (both limbs) and Cirkan (only left limb). Varices and anatomical scores did not change. CONCLUSIONS: ECS emerges as the most effective clinical treatment tested but improvements with Cirkan on vein diameter and CEAP class were also observed. Clinical scores improved due to pain relief and edema reduction (ECS). These findings point to a positive effect of Cirkan, suggesting that venotonic drugs should be taken into account in the treatment of CVD.

Use of microcirculatory parameters to evaluate clinical treatments of chronic venous disorder (CVD).

OBJECTIVES: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks. PATIENTS AND METHODS: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software. RESULTS AND CONCLUSIONS: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Enzymes, trophoblasts, and cancer: the afterlife of an idea (1924-2008).

In the early 20th century, advocacy of the enzyme therapy of cancer was primarily the work of one man, John Beard, DSc (1858-1924). He and his collaborators made a determined effort to establish this mode of therapy, especially in the years 1905 to 1911. Despite a brief flowering of international interest, Beard's efforts came to naught. During the 20th century, there was a succession of American researchers who continued to investigate this topic. This included Marshall William McDuffie, MD (1882-1945), Frank LeForest Morse, MD (1876-1953), Franklin Lloyd Shively, MD (1887-1971), and William Donald Kelley (1926-2005). In central Europe, India, and other parts of the globe, the use of pancreatic enzymes as an adjuvant treatment for cancer has become a fairly routine practice, at least among those doctors who utilize complementary and alternative medicine (CAM). It is also a well-established method for reducing inflammation and mitigating the adverse effects of cytotoxic treatment.

Efficacy of Wobe-Mugos E for reduction of oral mucositis after radiotherapy : results of a prospective, randomized, placebo-controlled, triple-blind phase III multicenter study.

PURPOSE: To investigate the efficacy and safety of Wobe-Mugos E (proteolytic enzymes) for amelioration of early side effects of radiotherapy for head-and-neck tumors, particularly oral mucositis. PATIENTS AND METHODS: The study was a prospective, randomized, multicenter, placebo-controlled, triple-blind phase III study with parallel groups. 69 patients with carcinomas of the oropharynx or the oral cavity were enrolled between 1996 and 2000 in five centers; 54 of these were recruited in Dresden. Of the 69 patients, 61 (Dresden: 46) were available for analysis. The proteolytic enzymes tested (Wobe-Mugos E) comprised papain 100 mg, trypsin 40 mg, and chymotrypsin 40 mg. RESULTS: Wobe-Mugos E was well tolerated. For the maximum mucositis scores, no statistically significant differences were found between the placebo and the verum group. The average mucositis score over weeks 1-6 revealed a significant difference in favor of the placebo arm, based on an earlier onset of mucositis in the Wobe-Mugos E group. CONCLUSION: The present study failed to demonstrate any effect of treatment with Wobe-Mugos E on radiotherapy side effects in patients treated for head-and-neck tumors. In particular, there was no beneficial effect on radiation-induced early oral mucositis.

Micronuclei evaluation of reduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer: an indian experience.

BACKGROUND: Lung cancer is the most common cancer in the world accounting for 17.6% cancers worldwide. The AAR i n I ndian population varies f r om 0.98-15.55. The aim of t he present study was to analyze areduction in neoadjuvant chemotherapy related acute toxicity in locally advanced lung cancer (stage IIIA and III B) using Wobe Mugos E and its evaluation using micronuclei as a cytogenetic marker. Micronuclei, which are cytoplasmic fragments of DNA, have been used as a biological dosimeter to assess DNA damage. MATERIAL AND METHODS: Fourty patients of locally advanced NSCLC were randomized into two study groups between 2001-2003. One group received neoadjuvant chemotherapy using Cisplatin and Etoposide. The other group received neoadjuvant chemotherapy using Cisplatin and Etoposide along with Wobe Mugos E which is a proteolytic enzyme preparation. A study of micronuclei frequency was done pre and post chemotherapy in both groups. RESULTS: Thirty eight patients were available for final evaluation. Anemia was the most common hematological toxicity observed. Nausea and vomiting were the most common non -hematological toxicity seen. Wobe Mugos E was found to reduce the incidence of leucopenia (p = 0.005), nausea (p=0.004), vomiting (p= 0.003), sensory neuropathy (p = 0.032) and treatment related depression (p= 0.005). A reduction in micronuclei was seen in patients in patients on Wobe Mugos E. (p =0.01). CONCLUSION: Neo-adjuvant chemotherapy related acute toxicity is a major problem in patients with advanced lung cancer. A reduction in micronuclei frequency shows Wobe Mugos E to be effective in reducing chemotherapy related acute toxicity.

Use of enzyme and heparin paste in acute haemorrhoids.

BACKGROUND: While treating acutely inflammed piles, surgeons in general prefer to stick to the conservative method of treatment. This includes bed rest in a Trendelenburg's or jack-knife position, administration of liquid diet, stool softeners, antibiotics, and anti-inflammatory drugs along with warm Sitz baths and local application of glycerin and magnesium sulphate paste. We introduced an additional method in treating acutely inflammed piles. Ten tablets of trypsin and chymotrypsin (Chymoral forte, Elder Pharmaceuticals India) were powdered and were mixed with 30 grams of heparin (Thrombophobe, German Remedies Ltd, Germany) ointment. This paste was applied to the inflammed pile mass. In all, 67 received this in patient treatment with an average hospital stay of 2 days. The results were compared using chi2 test with similarly placed 22 patients who were treated with the conventional method only. RESULTS: In the patients receiving the application of the enzyme paste, local pain was reduced to a great extent, the defecation was comfortable, there was negligible local pruritus, and the routine body movements of the patient were painless. Local signs observed in the form of the size of the piles, perianal edema, and tenderness, were also found to be significantly reduced. CONCLUSION: The results of this study demonstrate that the additional use of a heparin-enzyme paste applied directly over the pile masses significantly improves the healing and resolution of acutely inflammed hemorrhoids. The effectiveness of the traditional conservative method of treatment could be gainfully supplemented by use of the pharmaceutical preparation suggested in this study.