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References: Hair growth and hair loss

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In some cochlear pathologies, temporary hearing loss can be followed by complete or partial functional recovery. Our previous findings suggest the involvement of an excitotoxic (glutamate-related) disruption of inner hair cell (IHC)-auditory nerve synapses, followed by synaptic regeneration. It is essential to understand the molecular mechanisms responsible for this synaptic repair if new therapeutic strategies are to be developed. In guinea pig cochleas, acute synaptic excitotoxic damage (mimicking what occurs with acoustic trauma or local ischemia) is achieved by locally applying AMPA, a glutamate agonist. This results in a total disruption of all IHC-auditory dendrite synapses, together with a disappearance of cochlear potentials. Within the next 5 days, however, a recovery of both the normal pattern of IHC innervation and the physiological responses is observed. The fact that the blockage of the NMDA receptors during functional recovery delayed the regrowth of neurites and the restoration of hearing suggests that glutamate plays a neurotrophic role via activation of NMDA receptors. Experiments are in progress to investigate, among other factors, the role of other glutamate receptor subunits. A reversible in vivo antisense strategy is being developed to overcome the lack of specificity of some antagonists. First results bode well for future pharmacological therapies in cochlear pathologies where glutamatergic synapses are likely to be involved; i.e., noise trauma, ischemia-related sudden deafness, and neural presbycusis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9105452&dopt=Abstract

Genes Dev. 1997 Apr 15;11(8):996-1007.
Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation.

Kaya G, Rodriguez I, Jorcano JL, Vassalli P, Stamenkovic I.

Department of Pathology, University Medical Center, University of Geneva, Switzerland.

CD44 is a broadly distributed polymorphic glycoprotein that serves as the principal cell-surface receptor for hyaluronate. Although CD44-mediated cell interaction with hyaluronate has been implicated in a variety of physiologic events, including cell-cell and cell-substrate adhesion, cell migration, proliferation, and activation, as well as hyaluronate uptake and degradation, the biologic role of CD44 in vivo in various tissues remains to be determined. In the present work we have developed transgenic mice that express an antisense CD44 cDNA driven by the keratin-5 promoter. These mice lack detectable CD44 expression in skin keratinocytes and corneal epithelium and display abnormal hyaluronate accumulation in the superficial dermis and corneal stroma, distinct morphologic alterations of basal keratinocytes and cornea, and defective keratinocyte proliferation in response to mitogen and growth factors. These alterations are reflected by a decrease in skin elasticity, impaired local inflammatory response and tissue repair, delayed hair regrowth, and failure of the epidermis to undergo hyperplasia in response to carcinogen. Our observations indicate that two major functions of CD44 in skin are the regulation of keratinocyte proliferation in response to extracellular stimuli and the maintenance of local hyaluronate homeostasis.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9136928&dopt=Abstract

J Pediatr Surg. 2000 Nov;35(11):1623-5.
Tubed latissimus dorsi musculocutaneous flaps for esophageal replacement in puppies: long-term follow-up.

Yamataka A, Wang K, Kobayashi H, Segawa O, Miyahara K, Sueyoshi N, Miyano T.

Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan.

PURPOSE: The aim of this study was to show that a tubed latissimus dorsi musculocutaneous flap (tubed LDMCF) may be useful for treating circumferential esophageal defects. METHODS: A segment of esophagus 3 vertebrae long was excised through a right thoracotomy in each of 6 puppies, and a tubed LDMCF was interposed between the cut ends of esophagus. The puppies were sacrificed after a mean follow-up period of 6.6 years. The tubed LDMCF was examined histologically. Functional integrity was assessed using barium meal and endoscopy before sacrifice. RESULTS: All puppies survived and grew normally on a normal diet, although 4 vomited occasionally. There was smooth passage of barium through the tubed LDMCF without stenosis, although endoscopy showed regrowth of hair. Histologically, no metaplasia, dysplasia, or malignancy was observed in any tubed LDMCF. CONCLUSIONS: The tubed LDMCF is technically safe, obviates the necessity for laparotomy, and long-term follow-up would suggest that it is histologically stable. Thus, it could become an alternative procedure for bridging esophageal defects.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11083437&dopt=Abstract

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