Comparison of SGLT2 inhibitors vs. DPP4 inhibitors for patients with metabolic dysfunction associated fatty liver disease and diabetes mellitus.

PURPOSE: This study aimed to examine the potential benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) and diabetes mellitus (DM) using a real-world database. METHODS: We analyzed individuals with MAFLD and DM newly initiated on SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors from a large-scale administrative claims database. The primary outcome was the change in the fatty liver index (FLI) assessed using a linear mixed-effects model from the initiation of SGLT2 or DPP4 inhibitors. A propensity score-matching algorithm was used to compare the change in FLI among SGLT2 and DPP4 inhibitors. RESULTS: After propensity score matching, 6547 well-balanced pairs of SGLT2 and 6547 DPP4 inhibitor users were created. SGLT2 inhibitor use was associated with a greater decline in FLI than DPP4 inhibitor use (difference at 1-year measurement, - 3.8 [95% CI - 4.7 to - 3.0]). The advantage of SGLT2 inhibitor use over DPP4 inhibitor use for improvement in FLI was consistent across subgroups. The relationship between SGLT2 inhibitors and amelioration of FLI was comparable between individual SGLT2 inhibitors. CONCLUSIONS: Our analysis using large-scale real-world data demonstrated the potential advantage of SGLT2 inhibitors over DPP4 inhibitors in patients with MAFLD and DM.

A multi-centre, retrospective case series of oocyte cryopreservation in unmarried women diagnosed with haematological malignancies.

STUDY QUESTION: Is oocyte cryopreservation an applicable option for fertility preservation in unmarried patients with haematological malignancies? SUMMARY ANSWER: Oocyte cryopreservation via the vitrification method is accessible and may be considered an option for fertility preservation in unmarried patients with haematological malignancies. WHAT IS KNOWN ALREADY: Haematological malignancies are most commonly observed amongst adolescent and young adult women. Although the survival rate and life expectancy of those with haematological malignancies have improved, chemotherapy and radiotherapy may impair their reproductive potential. Oocyte cryopreservation is thus an ideal option to preserve their fertility. STUDY DESIGN SIZE DURATION: This study retrospectively evaluated 193 unmarried patients (age: 26.2 ± 0.4 years) with haematological malignancies, who consulted for oocyte cryopreservation across 20 different fertility centres in Japan between February 2007 and January 2015. The primary outcome measures were the oocyte retrievals and oocyte cryopreservation outcomes. The secondary outcome measures were the outcomes following oocyte warming for IVF. PARTICIPANTS/MATERIALS SETTING METHODS: The patients had commenced ovarian stimulation cycles via antagonist, agonist, natural and minimal methods for oocyte retrievals, defined according to the treatment strategy of each respective fertility centre. A vitrification method using the Cryotop safety kit was used for oocyte cryopreservation. ICSIs were used for insemination of warmed oocytes. The endometrial preparation method for embryo transfer was hormonal replacement therapy, except in the case of a patient who underwent a spontaneous ovulatory cycle. MAIN RESULTS AND THE ROLE OF CHANCE: Among 193 patients, acute myeloid leukaemia (n = 45, 23.3%) was most common, followed by acute lymphoid leukaemia (n = 38, 19.7%) and Hodgkin's lymphoma (n = 30, 15.5%). In total, 162 patients (83.9%) underwent oocyte retrieval, and oocytes were successfully cryopreserved for 155 patients (80.3%). The mean number of oocyte retrieval cycles and cryopreserved oocytes were 1.7 ± 0.2 and 6.3 ± 0.4, respectively. As of December 2019, 14 patients (9.2%) had requested oocyte warming for IVF. The survival rate of oocytes after vitrification-warming was 85.2% (75/88). The rates of fertilisation and embryo development were 80.0% (60/75) and 46.7% (28/60), respectively. Ten patients (71.4%) had successful embryo transfers, and seven live births (50.0%) were achieved. LIMITATIONS REASONS FOR CAUTION: This study was limited by its retrospective nature. Additionally, there remains an insufficient number of cases regarding the warming of vitrified oocytes to reliably conclude whether oocyte cryopreservation is effective for patients with haematological malignancies. Further long-term follow-up study is required. WIDER IMPLICATIONS OF THE FINDINGS: Oocyte retrieval and oocyte cryopreservation were accessible for patients with haematological malignancies; however, the number of oocyte retrievals may have been limited due to the initiation of cancer treatments. Acceptable embryonic and pregnancy outcomes could be achieved following oocyte warming; therefore, our results suggest that oocyte cryopreservation can be considered an option for fertility preservation in patients with haematological malignancies. STUDY FUNDING/COMPETING INTERESTS: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Prediction of outpatient visits and expenditure under the Universal Coverage Scheme in Bangkok using subscriber's attributes: A random forest analysis.

Objectives: There is limited evidence on methods to allocate budgets to healthcare providers under capitation schemes. The objective of this study was to construct and test models that predict outpatient visits and expenditure for each healthcare facility using subscriber data from the preceding year. Study design: We used the database of the Universal Coverage Scheme in Bangkok, Thailand that stores subscriber information and healthcare service utilization data. One-percent and ten-percent random samples of subscribers were selected as training and testing groups, respectively. Methods: Using data of the training group, we constructed a model using a random forest algorithm to predict outpatient visits and expenditure in 2017 from the 2016 data. The model was applied to the testing group and facility-level predicted number of visits and expenditure were compared with actual data. Results: The identically-structured training and testing groups consisted of 37,259 and 371,650 subscribers, respectively. Approximately 25% of subscribers utilized outpatient services. The R2 for models predicting facility-level utilization rate (visits/subscribers) and expenditure per subscriber in 2017 were 0.85 and 0.75, respectively. Conclusions: The model to predict outpatient visits and expenditure performed well. Such a prediction model may be useful for allocating budgets to healthcare facilities under capitation systems.

Omphalomesenteric cyst and patent urachus in a 29-year-old male

@#Small bowel obstructions are commonly caused by bowel adhesions from previous intra-abdominal surgeries.1 Bowel obstructions in adults that are caused by the presence of vestigial embryonic structures are unusual.2 Omphalomesenteric duct and urachus are primitive embryonic structures, which normally involute between the 5th and 12th week of gestation.3 4 Failure to involute leads to anomalies such as patent ducts and omphalomesenteric cysts.2 5 6 7 Omphalomesenteric duct remnants are present in at least 2% of the population.2 Among the urachal remnants, a patent urachus is less common, only accounting for 15% of the cases.8 Simultaneous occurrence of both remnants is rare.5 Diagnostic imaging, such as ultrasonography, is usually performed to facilitate planning for subsequent management of patients who present with chronic symptoms related to the persistence of these remnants.9 Computed tomography may also be done to determine the location, size and patency of ducts and cysts, while voiding cystourethrograms can be used to determine bladder wall involvement.8 However, among undiagnosed patients who present with acute bowel obstruction, the presence of these remnants is usually established intraoperatively during exploratory laparotomy. The approach to treatment involves excision of the remnants and appropriate surgical management of the bowel obstruction.1 2 5 6 10 11 Prognosis is often good with uneventful postoperative recovery.1 2 5 A 29-year-old male came to our emergency room complaining of generalized, vague abdominal pain, gradual abdominal distension, post-prandial vomiting of previously eaten food, obstipation, and fever within 48 hours before consultation. The patient did not report any history of weight loss or gastrointestinal symptoms prior to the onset of the present problem. On physical examination, the patient was tachycardic and showed signs of an acute abdomen. Digital rectal examination showed an empty rectal vault, with no masses or bleeding noted. Laboratory findings revealed leukocytosis at 18.3 x 103/µL and normal serum electrolyte levels. Upright and supine abdominal x-rays showed dilated bowel loops with thickened serosa and multiple air-fluid levels (Figure 1A, 1B). We did an exploratory laparotomy with a working diagnosis of complete intestinal obstruction. Intraoperatively, we noted torsion of the ileum (Figure 1C) around a band, which runs from the ileum approximately 80 cm from the ileocecal valve, to the umbilicus. The band, an omphalomesenteric remnant, contains a cyst measuring 10 x 4.7 x 3 cm. (Figure 1D). We also noted a patent urachus inferior to the omphalomesenteric remnant, connecting the bladder to the umbilicus (Figure 1E). We detorted the bowels manually, resected the portion of the ileum where the omphalomesenteric remnant was attached, and did a double-barrel ileostomy. We excised the urachal remnant and performed cystorrhaphy and umbilicoplasty. The patient had an unremarkable postoperative recovery. Ileal anastomosis was planned to take place around 6 weeks postoperatively. Given the unexpected intraoperative findings of persistent embryonic structures, we asked the patient postoperatively about history of related symptoms. The patient denied of recurrent urinary tract infections in the past, but he claimed to have intermittent umbilical wetness with non-foul-smelling discharge, which spontaneously resolved after a few years, when he was a teenager. Omphalomesenteric remnants can be a cause of intestinal obstruction in adults with no previous history of surgery. A history of symptoms related to the presence of the remnants is rarely elicited preoperatively. Excision of the remnants with appropriate repair of affected structures and adequate management of the intestinal obstruction usually resolves the problem.

Factors that predict in-hospital mortality in eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis associated with asthma, eosinophilia, and necrotizing vasculitis. EGPA is potentially life-threatening and often involves peripheral neuropathies, peptic ulcers, cerebral vessel disease, and cardiovascular disease. However, there is limited understanding of the prognostics factors for patients with EGPA. We investigated the clinical features and factors affecting patients' in-hospital mortality, using a national inpatient database in Japan. METHODS: We retrospectively collected data of EGPA patients who required hospitalization between July 2010 and March 2013, using the Diagnosis Procedure Combination database. We evaluated EGPA patients' characteristics and performed multivariate logistic regression analyses to assess the factors associated with in-hospital mortality. RESULTS: A total of 2195 EGPA patients were identified. The mean age was 61.9 years, 42.1% (924/2195) were male, and 41.6% (914/2195) had emergent admission. In-hospital deaths occurred in 97/2195 patients (4.4%). Higher in-hospital mortality was associated with age older than 65 years, disturbance of consciousness on admission, unscheduled admission, respiratory disease, cardio-cerebrovascular disease, renal disease, sepsis, and malignant disease on admission. Lower mortality was associated with female gender and peripheral neuropathies. CONCLUSIONS: Our study revealed the clinical features of EGPA patients who required hospitalization and the factors associated with their mortality. These results may be useful for physicians when assessing disease severity or treatments for hospitalized EGPA patients.

The modulation of large airway smooth muscle phenotype and effects of epidermal growth factor receptor inhibition in the repeatedly allergen-challenged rat.

Allergen challenges induce airway hyperresponsiveness (AHR) and increased airway smooth muscle (ASM) mass in the sensitized rat. Whether the remodeled ASM changes its phenotype is uncertain. We examined, in sensitized Brown Norway rats, the effects of multiple ovalbumin (Ova) challenges on ASM remodeling and phenotype and the role of the epidermal growth factor receptor (EGFR) in these processes. Rats were sensitized with Ova and challenged three times at 5-day intervals with phosphate-buffered saline or Ova and pretreated with the EGFR inhibitor AG-1478 (5 mg/kg) or its vehicle dimethyl sulfoxide. Ova challenges increased ASM mass in all-sized airways and in large airway mRNA expression of smooth muscle myosin heavy chain (sm-MHC), assessed by laser capture. Myosin light chain kinase and the fast myosin isoform SM-B mRNA expressions were not affected. Ova induced AHR to methacholine, and, based on the constant-phase model, this was largely attributable to the small airways and lung derecruitment at 48 h that recovered by 1 wk. The EGFR ligands amphiregulin and heparin-binding epidermal growth factor (HB-EGF) were increased in bronchoalveolar lavage fluid at 48 h after Ova exposure. AG-1478 inhibited AHR and prevented ASM growth. Epithelial gene expression of EGFR, HB-EGF, matrix metalloproteinase (MMP)-9, Gro-α, and transforming growth factor-ß was unaffected by Ova challenges. We conclude that EGFR drives remodeling of ASM, which results from repeated Ova challenge. Furthermore, the latter results in excessive small airway and, to a lesser degree, large airway narrowing to methacholine, and large airway gene expression of contractile protein is conserved.

Histological predictors of outcome in ependymoma are dependent on anatomic site within the central nervous system.

Ependymomas originate in posterior fossa (PF), supratentorial (ST) or spinal cord (SC) compartments. At present, grading schemes are applied independent of anatomic site. We performed detailed histological examination on 238 World Health Organization grade II and III ependymomas. Among PF ependymomas, the presence of hypercellular areas, necrosis, microvascular proliferation and elevated mitotic rate (all P < 0.01) were significantly associated with worse progression-free survival (PFS), while extensive ependymal canal formation was not (P = 0.89). Similar to the PF tumors, microvascular proliferation (P = 0.01) and elevated mitotic rate (P = 0.03) were significantly associated with worse PFS in the ST tumors. However, in contrast to PF tumors, extensive ependymal canals (P = 0.03) were associated with worse clinical outcome in ST ependymomas, but hypercellularity (P = 0.57) and necrosis (P = 0.47) were not. On multivariate Cox regression, after adjusting for relevant clinical variables, individual histological factors and a composite histological score remained significant among ST and PF ependymoma. In contrast to both PF and ST ependymoma, histological features were not found to be associated with PFS in SC tumors. Taken together, the clinical relevance of specific histological features in ependymoma appears to be related to the anatomic site of origin and suggests that site-specific grading criteria be considered in future classification systems.

Safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix.

The aloe vera plant has a long history of safe use for oral and topical applications. This publication describes safety studies conducted on a proprietary high-purity aloe vera inner leaf fillet preparation, Qmatrix. In a 13-week study in rats, Qmatrix was administered via gavage at 0, 500, 1000 and 2000 mg/kg body weight (bw)/day. There were no significant changes in food or water consumption, body weight, serum biochemistry or hematology at any of the doses tested. Sporadic, significant increases were observed in some of the measured urinalysis parameters; however, these variations were not treatment-related, as most were observed only in one sex, not dose-dependent and within historical control values. Organ weights were unaffected, except for a statistically significant, though not dose-dependent, increase in absolute and relative weights of the right kidney in males at 500 and 2000 mg/kg bw/day, respectively. Histopathological analysis revealed no abnormal signs. Qmatrix was non-mutagenic in an Ames test and a chromosomal aberration test at concentrations up to 10,000 microg/plate, and in an in vivo bone marrow micronucleus test at doses up to 5000 mg/kg bw/day. Based on these results, Qmatrix is not genotoxic in vitro or in vivo and; has an oral NOAEL greater than 2000 mg/kg bw/day following 90 days of oral exposure.

Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells.

BACKGROUND AND PURPOSE: The voltage-gated Na(+) channels (Na(v)) and their corresponding current (I(Na)) are involved in several cellular processes, crucial to metastasis of cancer cells. We investigated the effects of eicosapentaenoic (EPA), an omega-3 polyunsaturated fatty acid, on I(Na) and metastatic functions (cell proliferation, endocytosis and invasion) in human and rat prostate cancer cell lines (PC-3 and Mat-LyLu cells). EXPERIMENTAL APPROACH: The whole-cell voltage clamp technique and conventional/quantitative real-time reverse transcriptase polymerase chain reaction analysis were used. The presence of Na(v) proteins was shown by immunohistochemical methods. Alterations in the fatty acid composition of phospholipids after treatment with EPA and metastatic functions were also examined. KEY RESULTS: A transient inward Na(+) current (I(Na)), highly sensitive to tetrodotoxin, and Na(V) proteins were found in these cells. Expression of Na(V)1.6 and Na(V)1.7 transcripts (SCN8A and SCN9A) was predominant in PC-3 cells, while Na(V)1.7 transcript (SCN9A) was the major component in Mat-LyLu cells. Tetrodotoxin or synthetic small interfering RNA targeted for SCN8A and SCN9A inhibited metastatic functions (endocytosis and invasion), but failed to inhibit proliferation in PC-3 cells. Exposure to EPA produced a rapid and concentration-dependent suppression of I(Na). In cells chronically treated (up to 72h) with EPA, the EPA content of cell lipids increased time-dependently, while arachidonic acid content decreased. Treatment of PC-3 cells with EPA decreased levels of mRNA for SCN9A and SCN8A, cell proliferation, invasion and endocytosis. CONCLUSION AND IMPLICATIONS: Treatment with EPA inhibited I(Na) directly and also indirectly, by down-regulation of Na(v) mRNA expression in prostate cancer cells, thus inhibiting their metastatic potential.

The epidermal growth factor receptor mediates allergic airway remodelling in the rat.

The chronicity of bronchial asthma is attributed to persistent airway inflammation and to a variety of structural changes, or remodelling, that includes smooth muscle and goblet cell hyperplasia. To investigate the mechanisms of airway remodelling, the current authors used an established allergen (ovalbumin; OVA)-driven rodent model (the Brown Norway rat). Brown Norway rats were sensitised to OVA and challenged three times at 5-day intervals to evoke airway remodelling. The effects of an epidermal growth factor (EGF) receptor inhibitor, AG1478, and a cysteinyl leukotriene-1 receptor antagonist, montelukast, on epithelial and airway smooth muscle (ASM) cell proliferation in vivo in response to repeated OVA challenge were tested. Three challenges with leukotriene (LT)D(4) were given, to examine their effects on remodelling with and without AG1478 pretreatment. OVA challenges caused ASM hyperplasia, with an increase in mass, epithelial cell proliferation and goblet cell proliferation. AG1478 prevented the changes, as did montelukast. Multiple OVA challenges increased heparin-binding EGF-like growth factor but not EGF expression by airway epithelium. LTD(4) reproduced the changes in remodelling induced by OVA and this was blocked by AG1478. Allergen-induced airway epithelial and airway smooth muscle remodelling is mediated by cysteinyl leukotrienes via the cysteinyl leukotriene-1 receptor with downstream effects on the epidermal growth factor receptor axis.

Ferroelectricity driven by Y d0-ness with rehybridization in YMnO3.

We investigated electronic structure of hexagonal multiferroic YMnO3 using the polarization dependent x-ray absorption spectroscopy (XAS) at O K and Mn L(2,3) edges. The spectra exhibit strong polarization dependence at both edges, reflecting anisotropic Mn 3d orbital occupation. Moreover, the O K edge spectra show that Y 4d states are strongly hybridized with O 2p ones, resulting in large anomalies in Born effective charges on off-centering Y and O ions. These results manifest that the Y d(0)-ness with rehybridization is the driving force for the ferroelectricity, and suggest a new approach to understand the multiferroicity in the hexagonal manganites.

Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma.

PURPOSE: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. PATIENTS AND METHODS: Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation. RESULTS: At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. CONCLUSION: Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

Chronic appendicitis diagnosed preoperatively as an ovarian dermoid.

Recurrent right lower quadrant pain in young women can be a diagnostic dilemma. Chronic appendicitis is often mistakenly excluded from the differential diagnosis. In the present case, pelvic inflammatory disease was diagnosed in a 19-year-old woman with bilateral lower abdominal pain (greater on the right than the left), fever, and elevated white blood cell count. She was treated with intravenous antibiotics until resolution of symptoms. The pain recurred 1 month later, and the patient presented to our emergency department. At that time, she was afebrile and all laboratory results were normal or negative, aside from an elevated white blood cell count. Computed tomography suggested a right ovarian dermoid. At laparoscopy, however, the right tube and ovary were normal, and chronic appendicitis was confirmed. Although computed tomography is often accurate for delineating the cause of pelvic abnormality, it also may be misleading.

Orbital ordering in La0.5Sr1.5MnO4 studied by soft X-ray linear dichroism.

We found that the conventional model of orbital-ordering of 3x(2)-r(2)/3y(2)-r(2) type in the e(g) states of La0.5Sr1.5MnO4 is incompatible with measurements of linear dichroism in the Mn 2p-edge x-ray absorption, whereas these e(g) states exhibit predominantly cross-type orbital ordering of x(2)-z(2)/y(2)-z(2). LDA+U band-structure calculations reveal that such a cross-type orbital-ordering results from a combined effect of antiferromagnetic structure, Jahn-Teller distortion, and on-site Coulomb interactions.

Determination of the orbital polarization in YTiO3 by using soft X-ray linear dichroism.

We report measurements of linear dichroism in x-ray absorption at Ti L(2,3) edges of a Mott-insulating ferromagnet YTiO3, where orbital ordering occurs in the triply degenerate Ti 3d t(2g) states. Dichroic spectra and their integrated intensities are obtained for the incident electric field with polarizations parallel to a, b, and c axes. The comparison of the spectra with atomic multiplet calculations removes the ambiguity about the orbital polarization, i.e., the relative weights of |xy>, |yz>, and |zx> orbits, which are crucial for the origin of ferromagnetism. The result is consistent with the previous analysis of nuclear magnetic resonance in the Mizokawa-Fujimori scheme.

Tinea capitis due to Trichophyton soudanense in Cincinnati, Ohio, in internationally adopted children from Liberia.

Two sisters, ages 5 and 6 years, who were adopted from Liberia, presented in Cincinnati, Ohio, with tinea capitis. Fungal cultures grew Trichophyton soudanense, a dermatophyte rarely seen in North America. Both girls had multiple other infections. They responded well to therapy with oral griseofulvin and topical selenium sulfide. With the current increase in international travel and adoption, nonendemic dermatophyte infections such as this need to be recognized.

Hartree-Fock study of orbital magnetic moments in 3d and 5f magnets and X-ray magnetic circular dichroism.

The spin (Ms) and orbital magnetic moments (Mo) of the uranium 5f state in the ferromagnetic compound uranium sulfide (US) and of the cobalt 3d state in various transition-metal superlattices are calculated on the basis of a tight-binding model, in which the intra-atomic f-f or d-d multipole interaction is taken into account using the Hartree-Fock (HF) approximation. The parameters in the model are determined on the basis of available first-principles calculations. For US, the calculated ratio Mo/Ms and magnetic circular dichroism spectrum for U M4,5 absorption are in good agreement with the experimental results. Inclusion of the expectation values of the spin-off-diagonal operators in addition to the number operators in the 5f state is found to be crucially important when describing the 5f magnetic state. A difference in enhancement of Mo of the Co atom between the Co/Pd and Co/Cu superlattices is discussed on the basis of a semi-quantitative calculation, assuming ferromagnetism.

Inhibitory mechanism of aloe single component (alprogen) on mediator release in guinea pig lung mast cells activated with specific antigen-antibody reactions.

We previously reported that the glycoprotein extracted from aloe strongly inhibited the mediator releases caused by the activation of guinea pig lung mast cells. Therefore, this study aimed to purify a single component that has an antiallergic effect from crude aloe extract and then to assess the effects of aloe single component (alprogen) on the mechanism of mediator releases caused by the mast cell activation. We purified aloe extracts by using various columns. We also purified mast cells from guinea pig lung tissues by using enzyme digestion, rough and discontinuous density Percoll gradient. Mast cells were sensitized with IgG(1) (anti-ovalbumin) and challenged with ovalbumin. Histamine was assayed by using a fluorometric analyzer and leukotrienes by radioimmunoassay. [Ca(2+)](i) level was analyzed by using a confocal laser scanning microscope. Protein kinase activity was determined by the protein phosphorylated with [gamma-(32)P]ATP. The phospholipase D activity was assessed by the labeled phosphatidylalcohol. The amount of mass 1,2-diacylglycerol (DAG) was measured by the [(3)H]DAG produced when prelabeled with [(3)H]myristic acid. Phospholipase A(2) activity was determined by measuring the lyso-phosphatidylcholine released from the labeled phospholipids. Alprogen significantly decreased histamine and leukotriene releases and blocked completely Ca(2+) influx during mast cell activation. The protein kinase C and phospholipase D activities were decreased by alprogen in dose-dependent manner. Alprogen inhibited mass DAG formation and the phospholipase A(2) activity during mast cell activation. The data suggest that alprogen purified from aloe inhibits multiple signals as well as blocking Ca(2+) influx caused by mast cells activated with specific antigen-antibody reactions and that then the inhibition of histamine and leukotriene release follows.