A Non-antibacterial Chemically-modified Tetracycline Inhibits Mammalian Collagenase Activity

1987 ◽  
Vol 66 (8) ◽  
pp. 1310-1314 ◽  
Author(s):  
L.M. Golub ◽  
T.F. McNamara ◽  
G. D'Angelo ◽  
R.A. Greenwald ◽  
N.S. Ramamurthy
Keyword(s):  
Male Rats ◽  
Toxicity Tests ◽  
Collagenolytic Activity ◽  
Collagenase Activity ◽  
Chemically Modified ◽  
Chemically Modified Tetracycline ◽  
Skin Collagen ◽  
Clinical Advantage

Tetracyclines (including the semi-synthetic analogues, minocycline and doxycycline) are considered useful adjuncts in periodontal therapy because they suppress Gram-negative periodontopathogens. Recently, these antibiotics were found to inhibit mammalian collagenase activity, a property which may also be of therapeutic value. It has been suggested that the anti-collagenase properties of the tetracyclines are independent of their antibiotic efficacy. To advance this hypothesis further, we chemically converted tetracycline hydrochloride to its non-antimicrobial analogue, de-dimethylaminotetracycline. This chemically-modified tetracycline (CMT), although no longer an effective antibiotic, was found to inhibit the in vitro activity of collagenase from partially purified extracts of human rheumatoid synovial tissue and rachitic rat epiphysis. In a preliminary in vivo study, pathologically-excessive collagenase in skin and gingiva was induced by rendering adult male rats diabetic, and the oral administration of CMT to these rats significantly reduced the excessive collagenase activity in both tissues. Moreover, CMT administration did not affect the severe hyperglycemia in these rats but did prevent, at least in part, the diabetes-induced loss of body weight, skin weight, and skin collagen mass; these effects suggest a lack of toxicity in this animal model. A proposed clinical advantage of CMT over conventional tetracyclines, in the treatment of diseases characterized by excessive collagenolytic activity, is the lack of development of antibiotic-resistant micro-organisms during prolonged use. However, the consideration of clinical trials to support this hypothesis must await further laboratory and extensive toxicity tests.

Metallic Elements (Cu, Zn, Ni and Mn) Toxicity Effects Determination on a Fresh Water Fish Cyprinus Carpio (Common Carp) Laboratory Acclimatized

2017 ◽  
Vol 68 (8) ◽  
pp. 1711-1715
Author(s):  
Stefania Gheorghe ◽  
Gabriela Geanina Vasile ◽  
Cristina Gligor ◽  
Irina Eugenia Lucaciu ◽  
Mihai Nita Lazar
Keyword(s):  
Cyprinus Carpio ◽  
Aquatic Organisms ◽  
Control Fish ◽  
Toxicity Tests ◽  
Fresh Water Fish ◽  
Metallic Elements ◽  
Mn Toxicity ◽  
Vitro Effect

Metallic elements copper (Cu), zinc (Zn), nickel (Ni) and manganese (Mn) are some of the most commonly found in water and sediment samples collected from the Danube - Danube Delta. These elements are important as essential micronutrients, being normally present at low concentrations in biological organisms, but in high concentrations they become toxic with immediate and delayed effects. The role of this metals is still controversial, that�s why bioconcentration potential is so important. In this non-clinical study, we tested in vitro effect of heavy metals on carp, Cyprinus carpio, reproducing in vivo presence of Cu, Zn, Ni and Mn in the Romanian�s surface water. The toxicity tests were performed according to OECD 203 by detecting the average (50%) lethal concentration - LC50 on aquatic organisms (freshwater fish) at 96h. The results pointed out that, copper value for LC 50 at 96h was estimated as 3.4 mg/L (concentrations tested in the range of 0.1 - 4.75 mg/L). Zinc value for LC 50 at 96h was estimated as 20.8 mg/L (concentrations tested in the range of 0.028 � 29.6 mg/L). Nickel value for LC 50 at 96h was estimated as 40.1 mg/L (concentrations tested in the range of 0.008 - 84.5 mg/L). For manganese the mortality effects has recorded at LC 50 at 96h at estimated value higher than 53 mg/L (concentrations tested in the range of 0.04 - 53.9 mg/L). The accuracy of the testing metals concentration was insured by the screening of the dilution water, as well as food and control fish, acclimated in laboratory conditions.

scholarly journals Stamina-Enhancing Effects of Human Adipose-Derived Stem Cells

2021 ◽  
Vol 30 ◽  
pp. 096368972110354
Author(s):  
Eun-Jung Yoon ◽  
Hye Rim Seong ◽  
Jangbeen Kyung ◽  
Dajeong Kim ◽  
Sangryong Park ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cells ◽  
Locomotor Activity ◽  
Tissue Injury ◽  
Male Rats ◽  
Adipose Derived Stem Cells ◽  
Sprague Dawley ◽  
Serum Triglycerides

Stamina-enhancing effects of human adipose derived stem cells (hADSCs) were investigated in young Sprague-Dawley rats. Ten-day-old male rats were transplanted intravenously (IV) or intracerebroventricularly (ICV) with hADSCs (1 × 106 cells/rat), and physical activity was measured by locomotor activity and rota-rod performance at post-natal day (PND) 14, 20, 30, and 40, as well as a forced swimming test at PND 41. hADSCs injection increased the moving time in locomotor activity, the latency in rota-rod performance, and the maximum swimming time. For the improvement of physical activity, ICV transplantation was superior to IV injection. In biochemical analyses, ICV transplantation of hADSCs markedly reduced serum creatine phosphokinase, lactate dehydrogenase, alanine transaminase, and muscular lipid peroxidation, the markers for muscular and hepatic injuries, despite the reduction in muscular glycogen and serum triglycerides as energy sources. Notably, hADSCs secreted brain-derived neurotrophic factor (BDNF) and nerve growth factor in vitro, and increased the level of BDNF in the brain and muscles in vivo. The results indicate that hADSCs enhance physical activity including stamina not only by attenuating tissue injury, but also by strengthening the muscles via production of BDNF.

scholarly journals Properties of a bovine collagen type I membrane for guided bone regeneration applications

e-Polymers ◽  
2021 ◽  
Vol 21 (1) ◽  
pp. 210-221
Author(s):  
Igor S. Brum ◽  
Carlos N. Elias ◽  
Jorge J. de Carvalho ◽  
Jorge L. S. Pires ◽  
Mario J. S. Pereira ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Collagen Type ◽  
Mechanical Stability ◽  
Collagen Type I ◽  
Guided Bone Regeneration ◽  
Bone Volume ◽  
Male Rats ◽  
Toxicity Tests ◽  
Type I

Abstract Dental implant treatment requires an available bone volume in the implantation site to ensure the implant’s mechanical stability. When the bone volume is insufficient, one must resort to surgical means such as guided bone regeneration (GBR). In GBR surgery, bone grafts and membranes are used. The objective of this work is to manufacture and characterize the in vitro and in vivo properties of resorbable collagen type I membranes (Green Membrane®) for GBR. Membrane surface morphology was characterized by SEM and roughness was measured using an interferometric noncontact 3D system. In vivo skin sensitization and toxicity tests have been performed on Wistar rats. Bone defects were prepared in 24 adult male rats, filled with biomaterials (Blue Bone® and Bio Oss®) and covered with collagen membranes to maintain the mechanical stability of the site for bone regeneration. The incisions were closed with simple stitches; and 60 days after the surgery, the animals were euthanized. Results showed that the analyzed membrane was homogeneous, with collagen fiber webs and open pores. It had no sign of cytotoxicity and the cells at the insertion site showed no bone morphological changes. There was no tissue reaction and no statistical difference between Blue Bone® and Bio Oss® groups. The proposed membrane has no cytotoxicity and displays a biocompatibility profile that makes it suitable for GBR.

Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release

1985 ◽  
Vol 249 (3) ◽  
pp. E276-E280 ◽  
Author(s):  
W. S. Evans ◽  
R. J. Krieg ◽  
E. R. Limber ◽  
D. L. Kaiser ◽  
M. O. Thorner
Keyword(s):  
Female Rats ◽  
Male Rats ◽  
Gonadal Hormone ◽  
Base Line ◽  
Pituitary Cells ◽  
Intact Male ◽  
Castrate Male ◽  
Basal Release

The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Ontogeny of Angiotensin-II-Induced Prolactin Release in vivo and in vitro in Female and Male Rats

1994 ◽  
Vol 59 (1) ◽  
pp. 57-62 ◽  
Author(s):  
Graciela S. Díaz-Torga ◽  
Damasia Becú-Villalobos ◽  
Carlos Libertun
Keyword(s):  
Angiotensin Ii ◽  
Male Rats ◽  
Prolactin Release

scholarly journals Prolactin and Male Fertility: The Long and Short Feedback Regulation

2009 ◽  
Vol 2009 ◽  
pp. 1-13 ◽  
Author(s):  
M. K. Gill-Sharma
Keyword(s):  
Chromatin Condensation ◽  
Feedback Regulation ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Reproductive Hormones ◽  
Male Rats ◽  
Normal Men

In the last 20 years, a pituitary-hypothalamus tissue culture system with intact neural and portal connections has been developed in our lab and used to understand the feedback mechanisms that regulate the secretions of adenohypophyseal hormones and fertility of male rats. In the last decade, several in vivo rat models have also been developed in our lab with a view to substantiate the in vitro findings, in order to delineate the role of pituitary hormones in the regulation of fertility of male rats. These studies have relied on both surgical and pharmacological interventions to modulate the secretions of gonadotropins and testosterone. The interrelationship between the circadian release of reproductive hormones has also been ascertained in normal men. Our studies suggest that testosterone regulates the secretion of prolactin through a long feedback mechanism, which appears to have been conserved from rats to humans. These studies have filled in a major lacuna pertaining to the role of prolactin in male reproductive physiology by demonstrating the interdependence between testosterone and prolactin. Systemic levels of prolactin play a deterministic role in the mechanism of chromatin condensation during spermiogenesis.

IgG modulation in male mice with reproductive failure after prenatal inflammation

Reproduction ◽  
2021 ◽  
Author(s):  
Marina Izvolskaia ◽  
Vasilina Ignatiuk ◽  
Ayshat Ismailova ◽  
Viktoria Sharova ◽  
Liudmila Zakharova
Keyword(s):  
Positive Impact ◽  
Brain Structures ◽  
Peritoneal Macrophages ◽  
The Body ◽  
Male Rats ◽  
Male Mice ◽  
Prenatal Inflammation ◽  
Exposure In Vivo

Sexual performance in adult male rats is highly sensitive to prenatal stress which can affect the functionality of the reproductive system and various brain structures involved in modulating sexual behavior. The immunomodulatory effect of mouse IgG on reproductive maturity in male offspring after LPS exposure in vivo and in vitro was studied. Prenatal IgG injection (20 µg / mouse) had a positive impact on the puberty of male mice whose mothers were exposed to LPS (100 µg / kg) on the 12th day of pregnancy. The number of Sertoli cells were increased, whereas the body weight and the number of symplastic spermatids were decreased in offspring as compared to LPS-treated animals. Besides, IgG had a positive effect on altered hormone levels: reduced estradiol level on the 5th and 14th postnatal days and increased testosterone level on the 30th postnatal day in blood that led to an increased number of mounting attempts in sexually mature males. The cAMP-dependent pathway may be involved in the regulation of the LPS-induced inflammation. IgG reduced the increased level of cAMP in mouse peritoneal macrophages activated by LPS in vitro. IgG is able to modulate inflammation processes, but its exposure time is important.

scholarly journals Chemically Modified Synthetic microRNA-205 Inhibits the Growth of Melanoma Cells In Vitro and In Vivo

2013 ◽  
Vol 21 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
Shunsuke Noguchi ◽  
Junya Iwasaki ◽  
Minami Kumazaki ◽  
Takashi Mori ◽  
Kohji Maruo ◽  
...  
Keyword(s):  
Melanoma Cells ◽  
Chemically Modified

scholarly journals Solubility and ADMET profiles of short oligomers of lactic acid

ADMET & DMPK ◽  
2020 ◽  
Author(s):  
Daniela Dascălu ◽  
Diana Larisa Roman ◽  
Madalina Filip ◽  
Alecu Aurel Ciorsac ◽  
Vasile Ostafe ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Glucocorticoid Receptors ◽  
Degradation Products ◽  
Organic Anion ◽  
Toxicity Tests ◽  
Medical Applications ◽  
Eye Injuries ◽  
Toxicological Effects

<p class="ADMETkeywordsheading">Polylactic acid (PLA) is a polymer with an increased potential to be used in different medical applications, including tissue engineering and drug-carries. The use of PLA in medical applications implies the evaluation of the human organism's response to the polymer inserting and to its degradation products. Consequently, within this study, we have investigated the solubility and ADMET profiles of the short oligomers (having the molecular weight lower than 3000 Da) resulting in degradation products of PLA. There is a linear decrease of the molar solubility of investigated oligomers with molecular weight. The results that are obtained also reveal that short oligomers of PLA have promising pharmacological profiles and limited toxicological effects on humans. These oligomers are predicted as potential inhibitors of the organic anion transporting peptides OATP1B1 and OATP1B3, they present minor probability to affect the androgen and glucocorticoid receptors, have a weak potential of hepatotoxicity, and may produce eye injuries. These outcomes may be used to guide or to supplement in vitro and/or in vivo toxicity tests such as to enhance the biodegradation properties of the biopolymer.</p>

scholarly journals In vitro and in vivo Activities of Psidium guajava and Azadirachta indica Leaf Extracts and solvent Fractions against Salmonella Typhi

2021 ◽  
pp. 56-71
Author(s):  
Adetutu Adewale ◽  
Olaniyi Deborah Temitope ◽  
Awodugba Tamilore ◽  
Owoade Abiodun Olusoji ◽  
Olaniyan, Lamidi Waheed B. ◽  
...  
Keyword(s):  
Body Weight ◽  
Hematological Parameters ◽  
Sub Saharan Africa ◽  
Male Rats ◽  
Carrier Status ◽  
Leaf Extracts ◽  
Salmonella Infections ◽  
Neem Leaves

Typhoidal salmonella infections remain a challenge in the health care system in sub-Saharan Africa. Carrier status and advent of multi-drug resistant S. Typhi strains have necessitated the search for new drug leads. Hence, this study aims at investigating P. guajava and A. indica leaves for anti-salmonella activities. Guava and neem leaves were extracted by maceration in methanol and fractionated by solvent partitioning. In vitro activities were assessed by agar well diffusion and broth micro-dilution methods. Sixty male rats were randomized to 10 groups of 6 animals each for the in vivo experiments. Groups of rats except, normal control, were induced with 0.5McFarland of S. Typhi suspension orally. Treatment groups received 200 mg/kg body weight of extracts and fractions, and the control groups were treated with 14.29mg/kg body weight of ciprofloxacin and 1%v/v DMSO for 7 days post-infection. Biochemical parameters were determined spectrophotometrically. Hematological parameters were analyzed with automated hematology diagnostic machine. All fractions of P. guajava and three of A. indica inhibited S. Typhi growth with Zone of Inhibition (ZI) ranging from 11-15 mm. Active fractions inhibited 48.60-62.45% of S. Typhi biofilm formation at 25 mg/mL with Minimum Bactericidal Inhibitory Concentration (MBIC) of 0.39-12.5 mg/mL. All fractions improved body weight of treated rats and inhibited bacteremia at 44.75 and 95.94%. Hematological parameters improved in all fractions-treated rats. MDA was not significantly (p<0.05) altered in all groups. One fraction of P. guajava (ePg) lowered the elevated level in concentration of Nitric oxide (NO) while all fractions enhanced the lowered activity of SOD. Elevated (lactate dehydrogenase (LDH), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and bilirubin (BIL) were lowered by all fractions to various extents in treated rats. Fractions of P. guajava, and A. indica could be further considered for identification of active anti-salmonella principle(s).

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