A role for G protein-coupled receptor 137b in bone remodeling in mouse and zebrafish.

G protein-coupled receptor 137b (GPR137b) is an orphan seven-pass transmembrane receptor of unknown function. In mouse, Gpr137b is highly expressed in osteoclasts in vivo and is upregulated during in vitro differentiation. To elucidate the role that GPR137b plays in osteoclasts, we tested the effect of GPR137b deficiency on osteoclast maturation and resorbing activity. We used CRISPR/Cas9 gene editing in mouse-derived ER-Hoxb8 immortalized myeloid progenitors to generate GPR137b-deficient osteoclast precursors. Decreasing Gpr137b in these precursors led to increased osteoclast differentiation and bone resorption activity. To explore the role of GPR137b during skeletal development, we generated zebrafish deficient for the ortholog gpr137ba. Gpr137ba-deficient zebrafish are viable and fertile and do not display overt morphological defects as adults. However, analysis of osteoclast function in gpr137ba-/- mutants demonstrated increased bone resorption. Micro-computed tomography evaluation of vertebral bone mass and morphology demonstrated that gpr137ba-deficiency altered the angle of the neural arch, a skeletal site with high osteoclast activity. Vital staining of gpr137ba-/- fish with calcein and alizarin red indicated that bone formation in the mutants is also increased, suggesting high bone turnover. These results identify GPR137b as a conserved negative regulator of osteoclast activity essential for normal resorption and patterning of the skeleton. Further, these data suggest that coordination of osteoclast and osteoblast activity is a conserved process among vertebrates and may have similar regulation.

Femoral neck fracture is accompanied by local changes in the content of transforming growth factor-beta1, interleukin-1beta and collagenase activity.

The aim of the study was to evaluate the relationship between the time from femoral neck fracture and the content of transforming growth factor-beta1 (TGF-beta1), interleukin-1beta (IL-1beta) and collagenase activity in bone samples of the femoral neck. The material consisted of 42 cancellous bone samples from the femoral neck collected from patients after the femoral neck fracture during hip replacement procedure. The content of TGF-beta1, IL-1beta in bone samples was measured with the use of enzyme-linked immunoassay (ELISA) and collagenase activity was measured with spectrofluorimetry. The mean content of TGF-beta1/total protein was 2.29 pg/microg (range from 0.9 to 4.0). The mean content of IL-1beta was 4.93 fg/microg (range from 1.4 to 12.5). The mean activity of collagenase was 49.08 nU/microg (range from 5.6 to 113.7). The content of TGF-beta1 and IL-1beta decreased after the injury. In case of TGF-beta1 the difference was statistically significant (p<0.05). The activity of collagenase was statistically significantly increasing in relation to time from the fracture (p<0.05). We found no correlation between the content of TGF- beta1, IL-1beta and the activity of collagenase and the age and the sex of the patients. Also, no significant discrepancies were found between the examined cytokines in relation to the bone loss of the femoral neck according to Singh's scale. These results confirm mutual changes of activity between examined cytokines in the area of fractured bone.

Age-related decrease in the activity of collagenase in the femoral head in patients with hip osteoarthritis.

The aim of the study was to evaluate the relation between the activity of collagenase in the subchondral bone of the femoral head and the age of patients with hip osteoarthritis. Thirty-two patients were enrolled into the study. The mean age was 66 (range from 37 to 80 years). Bone samples of the femoral head were harvested during total hip replacement. The activity of collagenase was measured through spectrofluorimetry. We found statistically a significant correlation between collagenase activity in the bone and age. The mean activity of collagenase in younger patients (37-68 years) was 64.17 IU/microg. In older patients (69-80 years), the mean collagenase activity was 52.26 IU/microg. In patients with hip osteoarthritis the activity of collagenase in the subchondral bone of the femoral head tended to decrease with an increase in age.

The effect of xylitol on the stability and morphological parameters of tablets with sorbitol made by direct tabletting of formulation components.

Model tablets of polyols (sorbitol and xylitol) comprised 88% by mass, were produced using a direct compression method. Morphological and mechanical parameters of the model tablets were investigated ex tempore as well as after 12 and 24 months' storage. The effect of xylitol on selected morphological parameters of practical relevance during storage was estimated. The results obtained are a basis for further work on the use of polyols (sorbitol, xylitol and other sugar alcohols) in the production of oral forms of drugs, particularly buccal tablets.

[Pancreatic fistulas]. / Przetoki trzustkowe.

The aim of our study was retrospective analysis of causes and treatment results of pancreatic fistula. In years 1989-1996, 40 patients aged 14-74 years were treated for pancreatic fistula in the Department of Gastroenterologic Surgery of Medical University in Warsaw. The majority of patients (36 adults) were treated conservatively, with the use of parenteral nutrition, drainage and somatostatin (in case of 4 patients). The healing of pancreatic fistula occurred in 27 medically treated patients after 26 days of therapy (mean value), the remaining patients were treated surgically. The applied treatment was effective in 38 out of 40 cases, 2 patients died (5.0%) due to the complications not connected with pancreatic fistula. In our opinion, in early stages of treatment of pancreatic fistula the conservative therapy with the use of parenteral nutrition is the treatment of choice and elective surgery should be used in patients, in whom conservative treatment fails.

Release of denotivir from the dispersed systems. Part I. Properties of hydrogel vehiculum and availability of active substance from intravaginal form of drug.

The study aimed at obtaining intravaginal drug form containing denotivir was performed. Complete deformation time, as well as pharmaceutical availability of biologically active substance suspended in liquefied vehiculum were determined in vitro.

Some physico-chemical properties micelle--benzalkonium chloride (BAC) adduct on interface in selected eye drops.

In selected eye drops the value of surface tension coefficient delta 25 and critical micelle concentration (cmc) was determined. Calculation of the hydrophilic-lipophilic balance level (HLBcmc) and the solution of the surface state f.Am = K.T form of Gibbs equation enables the estimation of the type of action of micelle with lipid corneal epithelium. Particular attention has been paid to the forms of eye drops which contain benzalkonium chloride (BAC).

Tensides from the group of propylene oxide and ethylene oxide copolymers. Part XI. Solubilization of acetylsalicylic acid (ASA) by monomethoxypoly(ethylene glycol) (M-PEG) micelles.

The process of structural solubilization of acetyl salicylic acid (ASA) in a balanced system (weight-balanced) by micelles of monomethoxypoly(ethylene glycol)-s-CH3OCH2[CH2OCH2]n-CH2OH (M(r) = 350-5000) types and, for comparison, by those of F-68 and F-108 Pluronics, was investigated. The determined viscosity and hydrodynamic parameters ([eta], KH, M eta, Robs, omega) allowed for the calculation of solubilizing activity of monomethoxypoly(ethylene glycol) micelles-pi s(ASA). The results of the investigation point at monomethoxypoly(ethylene glycol)s as an excipient, which may help to obtain new drug delivery systems.

Tensides from the group of propylene oxide and ethylene oxide copolymers. X. Solubilization of acetylsalicylic acid by polyetherodiol micelles.

The process of structural solubilization of acetylsalicylic acid in balanced systems (weight-balanced) by micelles of Rokopols of 30p160 and 30p60 types and, for comparison, by those of F-68 and F-108 Pluronics was investigated. The determined viscosity and hydrodynamic parameters allowed for the calculation of solubilizing activity of polyetherodiol micelles--n(s(A)). The results of the investigation point at Rokopols as an excipient, which may help to obtain new drug delivery systems.

[Tensides from a group of propylene oxide and ethylene oxide copolymers. VII. Test of utilizing critical concentrations of micella (CMC), at levels of equal density hydro-lipophilic (HLB) and measures of macroparticles (Ro, omega) in bile "A" of healthy persons and patients]. / Tenzydy z grupy kopolimerów tlenku propylenu i tlenku etylenu. VII. Próba wykorzystania krytycznego steezenia micelarnego (cmc), poziomu równowagi hydro-lipofilowej (HLB) oraz wymiarów Makroczasteczek (R0, omega w zolci "a" zdrowychi i chorych do oceny Wlasciwosci litogenolitycznych polieterodioli.

Using the model systems of reference (nonionic surfactants of Pluronic and Rokopol type) bile "A" in healthy and ill subjects (cholelithiasis, states after cholecystectomy, catarrh, chronic duodenitis) was characterized using chosen viscosity parameters. The model experiments enable selective, preclinical estimation of solubilisation capacity of nonionic surfactants of Pluronic type and their Polish analogues Rokopols.