Identification of Small Molecule Inhibitors and Ligand Directed Degraders of Calcium/Calmodulin Dependent Protein Kinase Kinase 1 and 2 (CaMKK1/2).

CaMKK2 signals through AMPK-dependent and AMPK-independent pathways to trigger cellular outputs including proliferation, differentiation, and migration, resulting in changes to metabolism, bone mass accrual, neuronal function, hematopoiesis, and immunity. CAMKK2 is upregulated in tumors including hepatocellular carcinoma, prostate, breast, and gastric cancer, and genetic deletion in myeloid cells results in increased antitumor immunity in several syngeneic models. Validation of the biological roles of CaMKK2 has relied on genetic deletion or small molecule inhibitors with activity against several biological targets.

Arsenite suppression of involucrin transcription through AP1 promoter sites in cultured human keratinocytes.

While preserving keratinocyte proliferative ability, arsenite suppresses cellular differentiation markers by preventing utilization of AP1 transcriptional response elements. In present experiments, arsenite had a dramatic effect in electrophoretic mobility supershift analysis of proteins binding to an involucrin promoter AP1 response element. Without arsenite treatment, binding of JunB and Fra1 was readily detected in nuclear extracts from preconfluent cultures and was not detected a week after confluence, while c-Fos was detected only after confluence.

Oxygen-dependent differentiation of human keratinocytes.

Oxygen is an essential micronutrient. Unlike many internal tissues, human epidermis obtains much of its oxygen supply from the atmosphere (21% oxygen), and it ordinarily experiences higher oxygen levels than internal tissues (estimated approximately 5%). To test whether epidermal cell growth and differentiation depend upon this higher oxygen level, keratinocyte cultures were studied at 21, 5, and 2% oxygen concentrations.

[Erythromycin pharmacokinetics in children after rectal and oral administration].

Pharmacokinetics of erythromycin base was studied clinically in children not older than 14 years treated with new children dosage forms of the antibiotic i. e. 0.

[Preparation of crystals of chicken cytosolic aspartate amino- transferase, suitable for high resolution x-ray structural analysis].

The crystals of cytosolic chicken aspartate aminotransferase were grown from polyethylene glycol solutions. Two of the four crystal modifications obtained diffract to 1.8 A resolution.

[Rheological research in creating cellulose ester-based hydrogels with antibiotics].

Rheological properties of antibiotic hydrogels based on cellulose ethers were studied. It was shown possible to use methylcellulose and sodium carboxymethylcellulose as bases for hydrogels with erythromycin and fusidic acid.

[Rheological research in creating antibiotic hydrogels].

Experimental design was used in studying the effect of certain qualitative factors on rheological properties of antibiotic hydrogels. It was shown that water solubility of antibiotics and the procedure of their addition to gel bases were important in developing hydrogels. Scanning electron microscopy was used in comparative analysis of antibiotic hydrogels.

[Allergenic activity of mites of the genus Dermatophagoides].

The allergenic activities of the laboratory batches of D. farinae allergens have been studied by the methods of indirect mast-cell degranulation, neuroglial cytocrit, electrophoretic mobility changes. D.

[Sensitivity of the intestinal microflora of patients to antimicrobial preparations studied in order to conduct rational antibiotic treatment].

The oral administration of amikacin, ampiox, nystatin to CBA mice and the external treatment of the animals with 1% chlorhexidine solution makes it possible to create the germ-free state in the animals which must be then kept in a sterile box. If such animals receive the decantate of the patient's feces, introduced in a single administration, the microflora, which is subsequently formed in the intestine of the recipient animals, is identical to the donor's microflora. This permits the rapid and accurate determination of the sensitivity of the patient's intestinal microflora to different antimicrobial preparations and their combinations.

[Correction of intestinal microflora in chemotherapeutic dysbacteriosis using bifidobacterial and lactobacterial autologous strains].

The oral administration of kanamycin (40 mg/kg) or ampiox (500 mg/kg) to guinea pigs for 5 days led to disturbances in their normal intestinal microflora, manifested by a sharp decrease in the levels of lactobacteria and bifidobacteria, as well as by the appearance of large amounts of enterobacteria and enterococci, normally not detected in the proximal and distal sections of the intestinal tract. In adult volunteers receiving kanamycin orally in a dose of 40 mg/kg for 5 days disturbances in microbiocenosis also occurred: the amount of enterococci, staphylococci, lactobacteria and bifidobacteria considerably decreased, enterobacteria becoming the dominating microorganisms. Three oral administrations of bifidobacterial and lactobacterial autostrains immediately after the abolition of the antibiotic facilitated the rapid and effective restoration of the intestinal microflora.

[Experimental study of lincomycin ointment and gel].

The pharmacokinetics and safety of the lincomycin ointment and gel were studied. It was shown that diffusion of lincomycin through the skin was satisfactory. Investigation of their general toxicity and organotropic properties revealed neither irritating effect nor changes in the internal organs associated with the toxic effect of the drugs.

[Improved procedure for purification of aspartate transaminase from chicken heart cytosol. Characterization of the enzyme].

The purification procedure reported includes fractionation of water extract from chicken hearts with ammonium sulfate, fractional precipitation with ethanol, chromatography on Whatman CM-52 cellulose and crystallization. Specific activity of the pure crystalline enzyme was 234 micromoles.min-1.