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J Pathol. 1976 May;119(1):21-8.
Localisation and tissue effects of tritiated dehydroretronecine in young rats.

Shumaker RC, Hsu IC, Allen JR.

Sixteen male Spraque-Dawley rats were injected with 3H-dehydroretronecine. The rats were subsequently evaluated for gross and microscopic changes. Scintillation counts and autoradiographic studies of the various organs demonstrated that the pyrrole accumulates in organs which were shown here and by others (Peterson et al; Allen and Hsu) to be affected most severely by dehydroretronecine and dehydroheliotridine. In the present experiment 3H-dehydroretronecine was shown to decrease the growth rate of the rats, decrease the percentage of circulating neutrophils and alter the hepatic mitotic index. Histologically, accumulations of label were seen in the glandular region of the stomach, in the liver, in Huxley's and Henle's layers of the hair follicles and in the epithelial cells lining the convoluted tubules of the kidney. Scintillation counts on the various tissues and autoradiographic evaluations of tissue sections indicate that there is a preferential localisation of radioactivity in the gastric mucosa which is postulated to be related to the pH in this area.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=932871&dopt=Abstract




Biol Pharm Bull. 1997 Sep;20(9):969-72.
Hair analysis for drugs of abuse. XVIII. 3,4-Methylenedioxymethamphetamine (MDMA) disposition in hair roots and use in identification of acute MDMA poisoning.

Nakahara Y, Kikura R.

National Institute of Health Sciences, Tokyo, Japan.

Disposition of 3,4-methylenedioxymethamphetamine (MDMA) in hair roots was studied using rats and the hair root samples were evaluated to prove acute MDMA poisoning. The back hair of male pigmented hairy rats (n = 6) was shaved and 5 d later the animals were intraperitoneally administered with acute poisonous doses (20, 40, 60, 80 and 100 mg/kg) of MDMA. Roots of the hairs were then plucked out with a hair nipper 5 min and, 0.5, 1, 2, 6 and 24 h after injection. The hair root samples were, directly or after being washed with detergent, extracted with methanol-5 N HCl (20:1) under ultrasonication in ice-cold water for 4 h. After filtration and evaporation, the residue was derivatized with pentafluoropropionic anhydride and analyzed by GC/MS. From all samples including the 5 min sample, MDMA was detected at high concentrations (up to 156 ng/mg) accompanied by 3,4-methylenedioxyamphetamine (MDA). Some of the animals died within 2 h after administration, but in the surviving rats the MDMA concentrations in the hair roots increased up to 6 h and then slowly decreased until 24 h. The remaining MDMA after washing apparently increased from 13-31% at 0.5 h to 51-83% at 24 h in the surviving rats. These facts show that most of drugs in the hair roots are not yet immobilized in the early stage and are thereafter gradually incorporated into the hair shaft. Increase of the MDMA concentration stopped soon after death of the animal, probably due to the cessation of hair growth. Although the ratios of MDA/MDMA steadily increased over time, those after death plateaued, probably due to the cessation of metabolism after death. It was clearly shown that MDMA is more quickly incorporated into and more firmly retained in hair than methamphetamine (MA) by comparing their disposition in hair roots.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9331978&dopt=Abstract




J Neurosci. 1997 Nov 1;17(21):8270-82.
Analysis of rat vestibular hair cell development and regeneration using calretinin as an early marker.

Zheng JL, Gao WQ.

Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.

Despite increased interest in inner ear hair cell regeneration, it is still unclear what exact mechanisms underlie hair cell regeneration in mammals because of our limited understanding of hair cell development and the lack of specific hair cell markers. In this report, we studied hair cell development using immunohistochemistry on sections prepared from embryonic day (E) 13 to postnatal day 7 rat inner ear tissues. Of many epithelial, neuronal, and glial markers, we found that calcium-binding protein antibodies recognizing calretinin, calmodulin, or parvalbumin labeled immature hair cells in rat vestibular end organs. In particular, calretinin antiserum labeled the initial differentiating hair cells at E15, a stage immediately after the terminal mitosis of hair cell progenitors. The selective immunoreactivity of postmitotic presumptive hair cells, but not supporting cells or peripheral epithelial cells, was confirmed in utricular epithelial sheet cultures. Double labeling with calretinin and bromodeoxyuridine antibodies in long-term cultures showed that only a few mitotic utricular supporting cells became calretinin positive. Thus, although proliferation-mediated regeneration of new hair cells might directly contribute to hair cell regeneration in rat utricles after injury, it is very limited. In addition, double labeling with calretinin and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) revealed that differentiated hair cells underwent apoptosis during normal development at late embryonic and early postnatal stages in vivo and in vitro. Therefore, these experiments lay the groundwork for the time course of differentiation, regeneration, and apoptosis of mammalian vestibular hair cells. This work also suggests that calcium-binding proteins are useful markers for studies on inner ear hair cell differentiation and regeneration.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9334402&dopt=Abstract





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