Pharmacodynamic Activity of the Novel Neurokinin-3 Receptor Antagonist SJX-653 in Healthy Men.

Context: SJX-653 is a novel neurokinin 3 receptor (NK3R) antagonist. The NK3 pathway is a central regulator of gonadotropin releasing hormone (GnRH) secretion and has also been implicated in the generation of hot flashes. Therefore, decreases of luteinizing hormone (LH) and testosterone in men serve as sensitive pharmacodynamic (PD) markers of central NK3 antagonism.

High-resolution temporal profiling of the human gut microbiome reveals consistent and cascading alterations in response to dietary glycans.

Background: Dietary glycans, widely used as food ingredients and not directly digested by humans, are of intense interest for their beneficial roles in human health through shaping the microbiome. Characterizing the consistency and temporal responses of the gut microbiome to glycans is critical for rationally developing and deploying these compounds as therapeutics.

Methods: We investigated the effect of two chemically distinct glycans (fructooligosaccharides and polydextrose) through three clinical studies conducted with 80 healthy volunteers.

Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis.

Background: Zenpep (APT-1008) is a pancreatic enzyme product for the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF).

Methods: Zenpep and Kreon, both containing 25,000 lipase units, were compared in a randomised, double-blind, crossover, non-inferiority study for CF-associated EPI in patients aged ≥12years. Patients on a standardised diet and stabilised treatment were randomised to two treatment sequences: Zenpep/Kreon or Kreon/Zenpep.

Long-term experience with ZENPEP in infants with exocrine pancreatic insufficiency associated with cystic fibrosis.

The objective of our study was to determine whether infants with cystic fibrosis who developed exocrine pancreatic insufficiency in early infancy would tolerate long-term treatment with ZENPEP (pancrelipase) delayed-release capsules, containing 3000 US Pharmacopeia units of lipase/capsule, and demonstrate consistent long-term growth. The most common treatment-emergent adverse events were diarrhea, vomiting, and constipation (mild or moderate). At study completion, median weight-for-age percentiles increased from 22nd to 49th, median length-for-age percentiles increased from 36.

Use of a combination formulation of bismuth, metronidazole and tetracycline with omeprazole as a rescue therapy for eradication of Helicobacter pylori.

Background: Helicobacter pylori infection occurs in children and adults worldwide. Standard triple therapy of omeprazole, amoxicillin and clarithromycin (OAC) may not be optimal.

Aim: To evaluate quadruple therapy with bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride, given with omeprazole in H.

Efficacy of a novel pancreatic enzyme product, EUR-1008 (Zenpep), in patients with exocrine pancreatic insufficiency due to chronic pancreatitis.

Objectives: EUR-1008 (ZENPEP® [pancrelipase] Delayed-Release Capsules) delayed-release capsules is a novel, enteric-coated, porcine-derived pancreatic enzyme product. This study evaluated the efficacy and safety of 2 doses of ZENPEP in patients with chronic pancreatitis (CP) and exocrine pancreatic insufficiency (EPI).

Methods: The effect of ZENPEP on the coefficient of fat absorption (CFA) was investigated in a randomized, double-blind, dose-response, crossover study with placebo run-in (7-9 days) and 2 treatment periods (9-11 days) composed of a high dose (7 × 20,000 lipase units per day) and a low dose (7 × 5000 lipase units per day).

Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea: results from two vehicle-controlled, randomized phase III studies.

Background: Rosacea is a common, chronic dermatosis for which safe and effective new treatment options are needed.

Objective: The objective of these studies was to evaluate the efficacy, tolerability, and safety of a new formulation of 15% azelaic acid (15%) gel (AzA gel), for the topical treatment of moderate, papulopustular rosacea.

Methods: Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled studies were conducted using identical study designs, patient-selection criteria, and efficacy end points.

A randomized, controlled study of the safety and efficacy of topical corticosteroid treatments of sunburn in healthy volunteers.

Topical glucocorticosteroids are frequently used for the treatment of sunburn despite the scarcity of randomized, double-blind controlled trials to support this indication. This randomized, intra-individually controlled trial compared the efficacy and safety of two topical glucocorticosteroids, 0.1% methylprednisolone aceponate milk (MPA) and 0.

Do urea/ammonium lactate combinations achieve better skin protection and hydration than either component alone?

Twenty subjects with healthy skin were treated with the following formulations for two weeks: drug-free W/O vehicle, 5% ammonium lactate (CAS 52003-58-4) in W/O vehicle, 5% urea (CAS 57-13-6) in W/O vehicle, 3% ammonium lactate + 3% urea in W/O vehicle, 5% ammonium lactate + 5% urea in W/O vehicle. These formulations were applied in randomized order to 6 test areas on the forearms; one area was left untreated. Repetitive washings were additionally performed in the second treatment week.

Inhibitory effect of 1alpha,25-dihydroxyvitamin D3 on allogeneic lymphocyte stimulation and Langerhans cell maturation.

1alpha,25-Dihydroxyvitamin D3 (calcitriol) has been shown to inhibit the proliferation of peripheral blood mononuclear cells induced by allogeneic Langerhans cells in a human mixed epidermal cell lymphocyte reaction. The potent antigen-presenting function of Langerhans cells is gained during culture. We tried to dissect the effect of calcitriol on lymphocyte proliferation and Langerhans cell maturation in a murine mixed epidermal cell lymphocyte reaction using unfractioned epidermal cells as a source for Langerhans cells.

Potent gene regulatory and antiproliferative activities of 20-methyl analogues of 1,25 dihydroxyvitamin D3.

The biological active form of vitamin D3, 1,25-dihydroxyvitamin D3 (VD), regulates cellular growth and differentiation. This provides the hormone with an interesting therapeutic potential. However, hypercalcemia is a side effect, which is caused by VD's classical action, the regulation of calcium homeostasis.

1alpha,25-dihydroxyvitamin D3 rapidly inhibits fibroblast-induced collagen gel contraction.

1alpha,25-Dihydroxyvitamin D3 (1,25-D3) inhibits the proliferation of fibroblasts in vitro in monolayer culture. We investigated the effect of 1,25-D3 on normal murine and human fibroblasts cultured in collagen type I gels, which more closely resembles the in vivo situation in the dermis. In this culture system 1,25-D3 had no effect on fibroblast proliferation; however, the fibroblast-induced collagen gel contraction was inhibited in a time- and concentration-dependent manner in the nanomolar concentration range.

Synthesis and biological activities of 8(14)a-homocalcitriol.

8(14)a-Homocalcitriol was synthesized and tested for its biologic activities. It exhibited a vitamin D agonist activity profile. The compound was bound to the pig intestinal receptor with an affinity slightly less than calcitriol, showed the same potency in inducing HL 60 cell differentiation and inhibition of keratinocyte proliferation as calcitriol, and was found to be approximately 10-fold less potent in inducing hypercalcemia and hypercalciuria after a single injection in normal rats.

Effects of calcipotriol (MC 903) and calcitriol after topical application on the skin of hairless rats. Much lower effect of calcipotriol on systemic calcium homeostasis.

Topical application of calcitriol or its analogs is a new approach for treating psoriasis, but may be limited by systemic calcitropic effects. Calcipotriol (MC 903) is a novel calcitriol analog with low calcitropic potency after systemic application. To compare the topical potency of calcitriol and calcipotriol we applied the two drugs on the right flanks of hairless rats for 10 days.