Non-weight-bearing exercise attenuates papain-induced knee osteoarthritis in rats via the TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIM: Knee osteoarthritis (KOA) is characterized by joint wear and degeneration. Unfortunately, the medical community currently lacks effective treatment options for this disease. Suspension exercise therapy is considered an effective form of non-weight-bearing exercise for treating KOA. However, its mechanism of intervention in KOA is unclear. Therefore, this study aimed to evaluate the protective effects of non-weight-bearing exercise on rats with KOA and attempted to explore the underlying mechanisms. METHODS: In this study, a papain-induced KOA model was constructed, and the pathological changes in cartilage tissue were observed by hematoxylin and eosin (H&E) staining and scored according to the Mankin scoring principle. The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Reverse transcription-quantitative polymerase chain reaction and Western blotting were used to detect the expression of mRNA and proteins in the TLR4/MyD88/NF-κB signaling pathway. RESULTS: H&E staining and Mankin score data confirmed that non-weight-bearing exercise significantly improved articular cartilage degradation compared with that in the model group. Further, we observed that non-weight-bearing exercise differentially reduced serum levels of IL-1ß, IL-6, and TNF-α. Mechanistically, non-weight-bearing exercise downregulated gene and protein expression of TLR4, MyD88, and NF-κB in cartilage tissue. CONCLUSION: Non-weight-bearing exercise resulted in the progression of KOA by modulating the TLR4/MyD88/NF-κB signaling pathway and decreasing the levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α to slow down the degeneration of articular cartilage.

Development and clinical application of hydrogel formulations containing papain and urea for wound healing

Abstract Hydrogels are used for wound treatment, as they may contain one or more active components and protect the wound bed. Papain is one of the active substances that have been used with this purpose, alongside urea. In this paper, carboxypolymethylene hydrogels containing papain (2% and 10% concentrations) and urea (5% concentration) were produced. Physical-chemical stability was performed at 0, 7, 15 and 30 days at 2-8ºC, 25ºC and 40ºC, as well as the rheological aspects and proteolytic activity of papain by gel electrophoresis. Clinical efficacy of the formulations in patients with lower limb ulcers was also evaluated in a prospective, single-center, randomized, double-blind and comparative clinical trial. The results showed 7-day stability for the formulations under 25ºC, in addition to approximately 100% and 15% of protein activity for 10% and 2% papain hydrogel, respectively. The rheological profile was non-Newtonian for the 10% papain hydrogel tested. There were no significant differences regarding the mean time for healing of the lesions, although 10% papain presented a better approach to be used in all types of tissue present in the wound bed.

Papain and its inhibitor E-64 reduce camelid semen viscosity without impairing sperm function and improve post-thaw motility rates.

In camelids, the development of assisted reproductive technologies is impaired by the viscous nature of the semen. The protease papain has shown promise in reducing viscosity, although its effect on sperm integrity is unknown. The present study determined the optimal papain concentration and exposure time to reduce seminal plasma viscosity and investigated the effect of papain and its inhibitor E-64 on sperm function and cryopreservation in alpacas. Papain (0.1mg mL-1, 20min, 37°C) eliminated alpaca semen viscosity while maintaining sperm motility, viability, acrosome integrity and DNA integrity. Furthermore E-64 (10 µM at 37°C for 5min after 20min papain) inhibited the papain without impairing sperm function. Cryopreserved, papain-treated alpaca spermatozoa exhibited higher total motility rates after chilling and 0 and 1h after thawing compared with control (untreated) samples. Papain treatment, followed by inhibition of papain with E-64, is effective in reducing alpaca seminal plasma viscosity without impairing sperm integrity and improves post-thaw motility rates of cryopreserved alpaca spermatozoa. The use of the combination of papain and E-64 to eliminate the viscous component of camelid semen may aid the development of assisted reproductive technologies in camelids.

Effects of Balsamodendron mukul Gum Resin Extract on Articular Cartilage in Papain-induced Osteoarthritis.

Context • Osteoarthritis (OA) is one of the most prevalent chronic diseases of the musculoskeleton, causing functional disability among older adults. Management of OA includes conventional pharmacological treatments consisting primarily of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, physiotherapy, and surgical procedures. The medications are not ideal therapeutic agents; NSAIDs in particular can cause serious side effects. Objective • The study was conducted to investigate the effects of Balsamodendron mukul (BDM) gum resin extract on cartilage damage and microstructural changes in the subchondral bone of rats with papain-induced, osteoarthritic knee joints. Design • The authors designed a parallel randomized, controlled study to examine the effects of 3 concentrations of BDM on OA in a murine model. Setting • The present study was undertaken at the research laboratory, Faculty of Biological Engineering, Shobhit University (Modipuram, Meerut, India). Intervention • OA was induced by intra-articular injections of 0.2 mL of 4% papain solution and 0.1 mL of 0.03 M cysteine through the patellar ligament using a 26-gauge, 1.27-cm needle. The rats in the sham group received same volume of isotonic sodium chloride solution. The rats were divided into 6 groups : (1) control group-fresh rats, with ages and genders similar to those of the other groups but with no induction of OA and no treatments; (2) sham group-rats receiving a sham induction of OA using an intra-articular injection of saline of the same volume as the papain given to all OA rats but no treatments; (3) OA group-rats induced with OA but receiving no treatments; (4) OA + BDM (10%) group-rats induced with OA that received a 10% dose of BDM; (5) OA + BDM (20%) group-rats induced with OA that received a 20% dose of BDM; and (6) OA + BDM (40%) group-rats induced with OA that received a 40% dose of BDM. Rats in the treatment groups were fed their respective doses of BDM extract for 30 d. Outcome Measures • The articular cartilages from the knee joints and epiphyseal bones of the femur and tibia were extracted from the right- and left-side limbs to perform the biochemical, microarchitectural, and histological analyses. Results • The total protein and collagen content of the articular cartilage of the knees were significantly higher in all treated groups when compared with the OA group of rats. The histological analysis revealed a thicker cartilage and a higher trabecular density of the subchondral bone (epiphyseal bone) in BDM-treated rats. Conclusions • The oral dose of BDM gum resin extract was shown to relieve OA pain, regenerate the cartilaginous matrix, and increase the subchondral bone components. On the basis of the findings, the research team suggests that the BDM gum resin extract may be used for therapeutic interventions for reversal of OA and reduction in its related inflammatory pain.

Efeitos da papaína intramamária em vacas com mastite subclínica sobre a contagem de células somáticas e sólidos totais / Effects of intramammary papain in cows with subclinical mastitis on somatic cell count and total solids / Efectos de la papaína intramamaria en vacas con mastitis subclínica en recuento de células somáticas y sólidos totales

A mastite é a principal enfermidade que acomete o gado leiteiro. De todas as formas, a mastite subclínica é a que causa maiores perdas, na redução da produção, na diminuição da qualidade do leite e pelos altos custos de tratamento e descarte precoce de vacas. Altas contagens de células somáticas e baixo teor de sólidos totais no leite geralmente estão associados à mastite. Dessa forma, o objetivo deste estudo foi avaliar os efeitos de um creme de papaína a 2%, associado ou não ao cloridrato de ceftiofur (125mg) por via intramamária sobre a contagem de células somáticas e sólidos totais. O estudo foi realizado em 23 quartos mamários com mastite subclínica, detectadas pelo exame do CMT (California Mastitis Test) e da CCS (contagem de células somáticas), divididas em 4 grupos (1 ­ cloridrato de ceftiofur 125 mg; 2- cloridrato de ceftiofur 125mg + papaína 2%; 3- papaína 2%; 4- controle). As análises foram feitas com base no CMT, na CCS e de sólidos totais (ST) antes e após o tratamento. Os quartos mamários que foram tratados com papaína 2% tiveram alterações no leite, com catarro, grumos e coágulo com intensificação do quadro inflamatório. Não houve diferença significativa ao teste T entre as amostras antes e após o tratamento em nenhum dos grupos para as variáveis estudadas.(AU)

Mastitis is the main disease affecting dairy cattle. From all forms, subclinical mastitis is the one that causes the greater losses, with reduced production, decreased milk quality and by high treatment costs and early disposal of cows. High somatic cell counts and low total solids in milk are usually associated with mastitis. Thus, the aim of this study was to assess the effects of a intrammamarily 2% papain cream associated or not with ceftiofur hydrochloride (125mg) on somatic cell count and total solids. The study was performed on 23 breasts with subclinical mastitis, detected through CMT (California Mastitis Test) and SCC (somatic cell count), divided into 4 groups (1 - 125 mg ceftiofur hydrochloride, 2 - ceftiofur hydrochloride 125mg + 2% papain, 3 - 2% papain, 4 - control). The analyzes were based on CMT, SCC and total solids (TS) before and after treatment. The breasts that were treated with 2% papain presented changes in milk, with phlegm, lumps and clot with intensification of the inflammation. There were no significant differences between the T-test samples before and after treatment in either group for the studied variables.(AU)

La mastitis es la principal enfermedad que afecta el ganado lechero. La mastitis subclínica es la que causa grandes pérdidas en la reducción de la producción, disminución de la calidad de la leche, los altos costos de tratamiento y desecho precoz de vacas. Los altos recuentos de células somáticas y bajo contenido de sólidos totales en la leche están generalmente asociados con mastitis. Por lo tanto, el objetivo de este estudio fue evaluar los efectos de un 2% de papaína crema, con o sin el clorhidrato de ceftiofur (125 mg) por vía intramamaria en el recuento de células somáticas y sólidos totales. El estudio se realizó en 23 cuartos mamarios con mastitis subclínica, detectadas mediante el examen de la CMT (Prueba de Mastitis de California) y CCS (recuento de células somáticas), dividido en 4 grupos (1 - ceftiofur clorhidrato 125 mg; 2- clorhidrato de ceftiofur 125 mg + papaína 2%; 3- papaína 2%; 4 - control). Los análisis se basaron en CMT, en CCS y sólidos totales (ST), antes y después del tratamiento. Las glándulas mamarias que fueron tratadas con papaína 2% tuvieron cambios en la leche, con flema, grañones y coágulos con intensificación de inflamación. No hubo diferencia significativa por la prueba T, entre las muestras antes y después del tratamiento, en ninguno de los grupos para las variables estudiadas.(AU)

Spred1, a Suppressor of the Ras-ERK Pathway, Negatively Regulates Expansion and Function of Group 2 Innate Lymphoid Cells.

Cytokines from group 2 innate lymphoid cells (ILC2s) have been implicated in acute allergic responses, such as papain-induced lung inflammation. However, the means of homeostatic regulation of ILC2s have not been established. In this study, we demonstrated that Spred1, a negative regulator of the Ras-ERK pathway, plays an important role in the proliferation and apoptosis of ILC2s and in cytokine secretion from ILC2s. Intranasal administration of papain stimulated IL-5 and IL-13 production in the lung, which was enhanced when Spred1 was deleted. In vitro, Spred1(-/-) ILC2s proliferated faster than wild type ILC2s did and produced higher levels of cytokines in response to IL-33. On the contrary, a MEK inhibitor suppressed ILC2 proliferation and cytokine production. Spred1 deficiency resulted in stabilization of GATA3, which has been shown to play essential roles in the maintenance and cytokine production of ILC2. These data suggest that Spred1 negatively regulates ILC2 development and functions through the suppression of the Ras-ERK pathway.

[Effects of proteolytic enzyme therapy with Wobe Mugos against chemotherapy-induced toxicity in breast cancer patients - results of a pilot study]. / Proteolytische enzymtherapie mit wobe mugos gegen chemotherapie-bedingte toxizitäten bei brustkrebs-patientinnen - ergebnisse einer pilotstudie.

BACKGROUND: Wobe Mugos(®) is an enzyme preparation containing the proteases trypsin and papain from the pancreatic calf and commonly used in complementary medicine. From non-randomized studies, its multiple favorable effects including the reduction of adverse events from radiotherapy and chemotherapy in oncology patients have been reported. METHODS: Patients with invasive breast cancer receiving adjuvant or palliative chemotherapy between 2005 and 2006 and who were scheduled for at least two further cycles of this specific chemotherapy were included in this pilot study. A specific toxicity of at least grade 2 using the NCI common toxicity criteria which occurred during the preceeding cycle and was relevant to the patient was recorded. This specific toxicity, e.g. grade 2 emesis, was again evaluated after two analogously administered further chemotherapy cycles in which Wobe Mugos(®) had been coadministered. The hypothesis was that specific toxicites of individual patients will be reduced by this enzyme therapy. The majority of the 57 consecutive patients received palliative chemotherapy. Peroral enzyme therapy was coadministered with two uncracked coated tablets three times daily on all days of a chemotherapy cycle except on the day of chemotherapy administration. RESULTS: Tolerability was good. Positive and neutral effects on toxicity parameters were observed in 11 and 42 patients, respectively, and a negative influence in 4 women. CONCLUSION: We observed only a marginal influence of Wobe Mugos(®) in patients with breast cancer who had experienced at least a grade 2 toxicity in the preceding cycle and who received two further identical cycles of this chemotherapy in conjunction with the enzyme preparation. Randomized studies on homogenous patient populations are necessary.

[Effects of bone marrow mesenchymal stem cells transplantation on the apoptosis of alveolar wall cells in papain and Co60-induced pulmonary emphysema rats].

AIM: To study the effects of bone marrow MSCs transplantation on the apoptosis of alveolar wall cells and the expression of Bcl-2 and Bax of lung tissue in papain and Co60-induced pulmonary emphysema rats. METHODS: Female Lewis rats were randomly divided into three groups: control group, emphysema group, emphysema + MSCs transplantation group. Rats were sacrificed at days 14 and 28 after treatment. Morphologic analysis of the lung tissue was performed. The apoptosis of the lung cells was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of Bcl-2 and Bax were determined by immunohistochemical staining. RESULTS: Emphysematous changes of the lung tissue were observed in emphysema group and emphysema + MSCs transplantation group. However, the emphysematous change in emphysema + MSCs transplantation group was improved compared with the emphysema group. There was significant difference in the number of alveolar counted per unit area (MAN), mean alveoli area (MAA) and mean linear interval(MLI) between emphysema group and emphysema + MSCs transplantation group. The apoptotic index of the alveolar wall cells in emphysema + MSCs transplantation group was less than that in the emphysema group. The percentage of Bcl-2 positive cells in emphysema + MSCs transplantation group was significantly higher than that in the emphysema group. The percentage of Bax positive cells in emphysema + MSCs transplantation group was significantly lower than that in the emphysema group. The ratio of Bcl-2/Bax of emphysema + MSCs transplantation group was significantly higher than that in the emphysema group. CONCLUSION: Bone marrow MSCs transplantation inhibits the apoptosis of alveolar wall cells, upregulates the expression of Bcl-2 and downregulates the expression of Bax. This may be part of the reason that bone marrow MSCs transplantation improves the papain and Co60-induced pulmonary emphysema.

Aerosol probes of emphysema progression in dogs treated with all trans retinoic acid--an exploratory study.

This study used aerosol probes and lung function tests to investigate whether all trans retinoic acid (RA) can reverse experimental emphysema in dogs. Three dogs were evaluated with lung mechanics tests, including inspiratory capacity (IC), total lung capacity (TLC), and the ratio of forced expired volume in 0.5 sec to forced vital capacity (FEV0.5/FVC), an aerosol-derived measure of pulmonary airspace size (effective airspace diameter, EAD), and an aerosol-derived measure of nonuniform ventilation (aerosol dispersion, AD). Emphysema was induced by exposure to aerosolized papain. At 11 or 12 weeks post-papain exposure, dogs received oral RA (2 mg/kg/day) for 8 weeks, and were followed for an additional 4 weeks after stopping RA treatment. In all dogs, lung injury increased in the first 11-12 weeks following papain exposure, as evidenced by increasing trends of inspiratory capacity IC, TLC, EAD, and AD, and a decreasing trend of FEV0.5/FVC. These parameters of lung injury partially and transiently reversed their trends between 2 and 6 weeks following the initiation of RA treatment. A sham RA-treated group was not studied. However, similar reversals of lung injury were not seen in a previous study of dogs treated with papain but not RA, suggesting that RA altered emphysema progression in the current study. The limited reversal of lung injury in this study contrasts with more pronounced treatment effects seen in previous studies with rats. This paper discusses possible reasons for differences in these studies, as well as suggestions for improved experimental investigations of emphysema therapies.

Respiratory impedance following bronchoscopic or surgical lung volume reduction for emphysema.

BACKGROUND: Bronchoscopic methods for achieving lung volume reduction (BLVR) are presently undergoing clinical trials, and will soon be clinically available. Understanding the differential effects of surgical volume reduction therapy (LVRS) and BLVR on lung and chest wall physiology will assist physicians in selecting an optimal approach for patients. OBJECTIVES: Determine whether LVRS adversely affects lung or chest wall physiology at 3-month follow-up relative to BLVR in an experimental model of sheep emphysema. METHODS: Twelve mixed-breed sheep were treated with papain to produce experimental emphysema, and were divided into control, LVRS, and BLVR treatment groups. Lung and chest wall impedance was measured at 0, 5, and 10 cm H2O positive end-expiratory pressure at baseline and 3-month follow-up. RESULTS: Emphysema was associated with increased airway resistance, decreased lung tissue resistance and elastance, and increased chest wall tissue resistance. Following treatment, equivalent increases in lung elastance occurred in the LVRS and BLVR groups compared to controls. LVRS did not adversely affect chest wall impedance despite causing extensive pleural scarring. CONCLUSIONS: (1) Experimental emphysema following prolonged papain exposure progresses after cessation of treatment. (2) BLVR and LVRS produced equivalent lung and chest wall impedance responses at 3-month follow-up. (3) LVRS did not adversely affect chest wall impedance despite being associated with extensive pleural scarring.

A new, simple stapling technique for pulmonary emphysema: its effects and safety for improving respiratory function.

PURPOSE: We performed lung volume reduction surgery (LVRS) in an experimental model using a simple stapling technique (SST) for pulmonary emphysema. The technique uses a stapler to isolate the affected lung from the remaining lung instead of removing it. We performed the present experiment using dogs to study the effects and safety of LVRS using the SST. METHODS: Pulmonary emphysema was induced in 12 dogs with papain. They were divided into three groups: those operated on with SST composed the operation (Op) group; those receiving an experimental thoracotomy composed the sham-operation (Sham-op) group; and those not operated on composed the nonoperation (Non-op) group. Respiratory function was compared among the groups before induction of emphysema (baseline), after induction of emphysema (preoperation), and at 8 weeks after the operation (postoperation Op and Sham-op groups only). The lung was removed and histologically examined 8 weeks after the SST operation. RESULTS: In the Op group, alteration in forced expiratory volume (FEV) 0.5%, airway resistance (Raw) and specific airway conductance (sGaw) showed significantly favorable results. Histologically, the isolated area was widely replaced by fibrous tissue with numerous blood vessels in the circumference in the Op group; no signs of infection such as polykaryoleukocytes or microabscesses were observed in any of the samples. CONCLUSION: The LVRS for pulmonary emphysema using a simple stapling technique improved the expiratory flow and alleviated airway resistance. The isolated remaining lung was well organized without any infectious events or secondary adversity, thus demonstrating the safety of this technique. From these results, this technique is therefore suggested to be effective and applicable to clinical use.

Retrolective cohort study of an additive therapy with an oral enzyme preparation in patients with multiple myeloma.

PURPOSE: To evaluate the impact of an additive therapy with an oral enzyme (OE) preparation given for more than 6 months additionally to standard combination chemotherapy (vincristine/melphalan/cyclophosphamide/prednisone (VMCP)- or methylprednisolone/ vincristine/CCNU/cyclophosphamide/melphalan (MOCCA)-regimen) in the primary treatment of patients with multiple myeloma stages I-III. METHODS: A cohort of 265 patients with multiple myeloma stages I-III was consecutively treated at our institution in two parallel groups (control group (n = 99): chemotherapy +/-OE for less than 6 months; OE-group (n = 166): chemotherapy + OE for more than 6 months). The median follow-up time in the stages I, II, and III for the OE-group was 61, 37, and 46.5 months, respectively; for the control group the respective values were 33, 51.5, and 31.5 months. The primary endpoint of the study was disease-specific survival. Secondary endpoints were response to therapy, duration of first response and side effects. The chosen method for evaluation was the technique of a retrolective cohort analysis with a concurrent control group. Survival analysis was performed by the Kaplan-Meier method and multivariate analysis was done with the Cox proportional hazards model. RESULTS: Significantly higher overall response rates and longer duration of remissions were observed in the OE-group. Primary responders showed a longer mean survival time than non-responders. Additive therapy with OE given for more than 6 months decreased the hazard of death for patients at all stages of disease by approximately 60%. Observation time was not long enough to estimate the median survival for patients at stages I and II; for stage III patients it was 47 months in the control group versus 83 months for the patients treated with OE (P = 0.0014) which means a 3-year gain of survival time. Significant prognostic factors for survival, in the Cox regression analysis, were stage of disease and therapy with OE. The OE-therapy was generally well tolerated (3.6% of patients with mild to moderate gastrointestinal symptoms). CONCLUSION: OEs represent a promising new additive therapy in multiple myeloma which will be further evaluated in a randomized phase III trial in the USA.

Impact of complementary oral enzyme application on the postoperative treatment results of breast cancer patients--results of an epidemiological multicentre retrolective cohort study.

PURPOSE: [corrected] To evaluate the impact of postoperative treatment with an oral enzyme (OE) preparation given complementary to an antineoplastic therapy in patients with breast cancer. METHODS: The design of this epidemiological study was a retrolective cohort analysis with parallel groups. Design and conduct of the study were performed to current standards for prospective, controlled clinical trials. A cohort of 2,339 breast cancer patients undergoing surgical intervention and radio-, chemo- or hormonal therapy were studied in 216 centres. Of the 2,339 patients, 1,283 received complementary treatment with OE and 1,056 did not receive OE. Patients with other complementary medications were excluded and the final analysis was performed with the data from 649 patients, of whom 239 (37%) were additionally treated with OE (test group) and 410 (63%) without OE (control group). The median follow-up time for the test group was 485 days and for the control group 213 days. The primary endpoint of the study was to determine whether complementary treatment with OE can reduce typical disease- or therapy-associated signs and symptoms (gastrointestinal symptoms, mental symptoms, dyspnoea, headache, tumour pain, cachexia, skin disorders, infections, and side effects associated with the antineoplastic therapy) in patients with breast cancer. Imbalances for causal effects (covariates) were adjusted for by means of the propensity score. Outcome analysis was performed by estimating the linear regression between change in symptom score and propensity score with all data and using this regression line to calculate the change in symptom score which would be expected for each patient. Tumour-associated events (recurrence, metastasis, and death) were evaluated in terms of the number of events observed and time to event. The safety of treatment with OE was analysed in terms of the number and severity of adverse events, their duration, treatment and outcome. RESULTS: For all symptoms except tumour pain, the adjusted mean improvement in symptom scores was larger in the test group than in the control group. The adjusted difference was statistically significant for all symptoms, except tumour pain and infections. The results show that the typical disease- and therapy-associated signs and symptoms in patients on complementary therapy with OE during postoperative treatment were significantly less. For 75% of the test group and 55% of the control group the physician recorded "no signs and symptoms". A clear reduction in the side effects of radiotherapy and chemotherapy was documented in 74% of the test group and 55% of the control group. Analysis of survival, recurrence, and metastasis demonstrated a reduced number of events in the test group. There was evidence of a beneficial influence of OE on time to event, although the median observation time was too short in these breast cancer patients to draw definite conclusions. The safety component was judged in 98% of the test group and 76% of the control group as "very good" or "good". In the total sample of 2,339 patients, the rate of OE-associated adverse reactions was 3.2%. All side effects were mild to moderate gastrointestinal symptoms. CONCLUSION: Complementary treatment of breast cancer patients with OE improves the quality of life by reducing signs and symptoms of the disease and the side effects of adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that the patients may also gain benefit by a prolongation of the time to event for cancer recurrence, metastasis and survival. OE was generally well tolerated.

Hemostasis in raw peritoneal surfaces by combined use of sodium carboxymethylcellulose and papain for prevention of adhesions in the rat

A associacao de carboximetilcelulose sodica (CMC) e Papaina (PP), ja demonstrada como inibidora da formacao de aderencias peritoniais, e estudada em ratos quanto a seus possiveis efeitos sobre a hemostasia espontanea em areas cruentas do peritonio. A acao proteolitica da PP sobre a fibrina, que explica seu efeito anti-aderencia, nao se fez presente nem "in vivo", nem "in vitro" sobre coagulos pre-formados e ainda permitiu a formacao de coagulo "novo". Este comportamento e atribuido a outra acao da PP, semelhante a da trombina, de coagular fibrinogenio por cisao de seus fibrinopeptidios terminais. Concluiu-se que o emprego da associacao CMC-PP para previnir a formacao de aderencias peritoneais possa apresentar seguranca para uso em clinica humana, embora novos estudos devam ser ainda realizados.

Efeito de antiinflamatórios enzimáticos (bromélina, escina e papaína) no desenvolvimento de crânios e fêmures de ratas / The effect of enzymatic anti-inflammatory drugs (bromelain, aescin, and papain) on the development of skull and femur of rats

Neste trabalho estudou-se p efeito de antiinflamatórios enzimáticos de origem vegetal (bromelina, escina e papaína) no desenvolvimento de crânios e fêmures de ratas. Os antiinflamatórios foram injetados intraperitonealmente, em doses terapêuticas, em ratas prenhas e em filhotes (desde o desmame até atingirem a maturidade óssea - subgrupos IIB, IIIB e IVB). As três drogas antiinflamatórias de origem vegetal - bromelina, escina e papaína - causaram reduçäo do crescimento de crânios e fêmures de ratas

Induction of osteoarthrosis in the guinea pig knee by papain.

The main purpose of this investigation was to develop a model for experimental induction of osteoarthrosis. A previously described method using papain was tried on guinea pig knee joints. Eighteen adult guinea pigs were given papain intra-articularly in the right joints; the left joints were used as controls. The animals were killed after 6 hours, 1 week, 2 weeks, 2 months, 4 months, 6 months, 8 months, and 10 months. Specimens of the articular cartilage were removed for histologic and histochemical investigation. Microscopic surface irregularities could be observed in the animals after 6 hours, 1 week, and 2 weeks, and again after 8 and 10 months. Histochemical examination of the sections from the experimental joints indicated a loss and degradation of the sulfated glycosaminoglycans. This loss was evident after 6 hours, 1 week, 2 weeks, and 8 months. The first osteoarthrotic changes were observed macroscopically after 8 months. Radiographic changes in the experimental joints could be observed in all animals killed after 10 months. It was concluded that osteoarthrosis similar to that occurring in humans can be induced by this method.

[Occupational asthma. New findings on work related obstructive respiratory diseases (author's transl)]. / Berufsasthma. Neuere Erkenntnisse über beruflich bedingte obstruktive Atemwegserkrankungen.

In baker's asthma, however not in case of sensitization by pelage and epithelia of animal origin, the definite, concordant result of skin test and radio-allergosorbent test (RAST) renders inhalative provocation test under the conditions of working place. Clinical observations have shown persulfates and papain to cause occupational obstructive airway disease. The irritant gas ozone produces an increase in reactivity of the bronchial tree already in the range from 0.3 ppm onwards. Among 195 workmen exposed to isocyanates in the manufacture of plastic materials, 55 suffered from attacks of asthma attributable to the isocyanate exposure. One third of 99 persons investigated, who had manufactured or fed fish food prepared from Chironomus larvae, revealed clinically relevant sensitization of the respiratory tract to hemoglobin molecules contained in these larvae. In fragments of one of these hemoglobins (CCT VI) it was possible to locate four antigen determinants.

Pulmonary disease in workers exposed to papain: clinico-physiological and immunological studies.

Of the twenty-three employees at a pharmaceutical plant manufacturing a new product containing papain, twelve had respiratory symptoms of cough, wheezing, dyspnoea, or chest paint. Most were studied with in-depth interviews by a doctor, extensive pulmonary function tests, and immunoserological tests for IgE and precipitating antibodies specific for papain, as well as total IgE antibodies to common natural allergens. There were significant correlates (all P values < 0.05) between the presence of specific IgE antibodies to papain and decreases of FEV1, FEF75--85, TLC, RV, and response to bronchodilators as percentage change from baseline for all spirographic flow rates. Atopic workers developed pulmonary symptoms and antipapain antibodies significantly sooner after papain exposure than did the others. Duration of exposure had no effect on symptomatology, pulmonary function, or immunological response. However, those judged to have the greatest amount of dust exposure per work-day had significantly more pulmonary symptoms (P < 0.005). Papain produced lung diseases by acting as an inhalant allergen rather than a proteolytic enzyme. Papain is a potent sensitizer in humans for the production of respiratory disease. The pulmonary reactions, based on physiological data, seem to involve small airways, alveolar, and interstitial lung tissue in an inflammatory rather than destructive manner, and thus resemble bronchitis and interstitial lung disease rather than pulmonary emphysema or typical bronchial asthma.