Biomedical subjects

Z Shen

Publications and source records attributed to Z Shen.

At least 163 records · Page 9Linked to original sources

PubMed1998

Chondroadherin expression changes in skeletal development.

Chondroadherin is a cartilage protein with cell binding properties. The expression of chondroadherin was studied in rat tissues and during postnatal femoral head development. For design of oligonucleotide probes and primers a 1664 bp, full length, rat chondroadherin cDNA was isolated from a rat chondrosarcoma library and sequenced. Northern blot analysis showed chondroadherin mRNA to be present in femoral head and rib cartilage, as well as in tendon. More sensitive reverse-transcriptase PCR additionally identified the mRNA in calvaria, long bone and bone marrow. Localization of chondroadherin by immunocytochemistry in the developing femoral head from postnatal day 14 to day 60 showed presence of the protein in cartilaginous regions. With increasing age a very distinct localization of chondroadherin was seen in the territorial matrix around late proliferative cells in the growth plate as well as in the developing articular cartilage in the maturing femoral head. Localization of chondroadherin mRNA by in situ hybridization was in agreement with immunocytochemistry with strong hybridization signals in late proliferative cells in the growth plate. In the articular cartilage the expression was restricted to cells in the lower regions. A three-fold increase of cartilage chondroadherin content in the growing femoral head was demonstrated by Western blot analysis. The high expression of this cell binding protein in a dynamic region of cartilage suggests an important role for chondroadherin in the regulation of chondrocyte growth and proliferation.

Amino Acid Sequence↗

PubMed1998

A central region of Ku80 mediates interaction with Ku70 in vivo.

Ku, the DNA binding component of DNA-dependent protein kinase (DNA-PK), is a heterodimer composed of 70 and 86 kDa subunits, known as Ku70 and Ku80 respectively . Defects in DNA-PK subunits have been shown to result in a reduced capacity to repair DNA double-strand breaks. Assembly of the Ku heterodimer is required to obtain DNA end binding activity and association of the DNA-PK catalytic subunit. The regions of the Ku subunits responsible for heterodimerization have not been clearly defined in vivo . A previous study has suggested that the C-terminus of Ku80 is required for interaction with Ku70. Here we examine Ku subunit interaction using N- and C-terminal Ku80 deletions in a GAL4-based two-hybrid system and an independent mammalian in vivo system. Our two-hybrid study suggests that the central region of Ku80, not its C-terminus, is capable of mediating interaction with Ku70. To determine if this region mediates interaction with Ku70 in mammalian cells we transfected xrs-6 cells, which lack endogenous Ku80, with epitope-tagged Ku80 deletions carrying a nuclear localization signal. Immunoprecipitation from transfected cell extracts revealed that the central domain identified by the GAL4 two-hybrid studies stabilizes and co-immunoprecipitates with endogenous xrs-6 Ku70. The central interaction domain maps to the internally deleted regions of Ku80 in the mutant cell lines XR-V9B and XR-V15B. These findings indicate that the internally deleted Ku80 mutations carried in these cell lines are incapable of heterodimerization with Ku70.

Amino Acid Sequence↗

PubMed1998

Electrophoretic affinity chromatography: method validation.

A new method for preparative-scale separation of biomolecules, electrophoretic affinity chromatography (EAC), is proposed in this paper. Separation by EAC is carried out in a long and ribbon-like multicompartment electrolyser separated by membranes, in which the two central compartments are used for packing the gel matrix and for sample loading respectively. Next to the central compartments are the elution compartments and electrode compartments. The electric field is applied perpendicular to the fluid flow in the compartments. Adsorption and desorption steps may both be carried out in the presence of an electric field, which transports the target components into the gel compartment for adsorption and the impurities into the elution compartments for washing. After the adsorption step an elution solution is introduced and the product is released from the gel matrix and washed out. Separation of human serum albumin (HSA) from human serum gives HSA product of high purity, as demonstrated by isoelectric focusing analysis. The characteristics of electrophoretic binding of HSA on Blue Sepharose Fast Flow are examined. The preliminary results show that this new method has advantages in terms of high rate of mass transfer and ease of scaling up, which are of particular interest when large-scale separation of biomolecules is considered.

Adsorption↗

PubMed1998

Subtyping of transferrin by isoelectric focusing in immobilized pH gradients.

Isoelectric focusing in immobilized pH gradients ranging from pH 5.05 to 5.60 was used to study the distribution of transferrin (Tf) subtypes and their gene frequencies from 188 unrelated healthy donors of the Han population in Beijing. Six phenotypes (TfC1, TfC2, TfC1C2, TfC1C3, TfC1Dchi and TfC2Dchi) were detected and Tf*C3 has never before been reported in the Han population. Gene frequencies were as follows: Tf*C1 = 0.7420, Tf*C2 = 0.2420, Tf*C3 =0.0027, Tf*Dchi = 0.0133. There is good agreement between the observed and expected values corresponding to the Hardy-Weinberg equilibrium (sum (chi2) = 0.9183, df = 2, 0.5 < P < 0.75). The allele frequencies for Tf*C1, Tf*C2 and Tf*Dchi agreed with those previously reported for the Chinese Han population.

Humans↗

PubMed1998

Phorbol 12-myristate 13-acetate stimulates lysophosphatidic acid secretion from ovarian and cervical cancer cells but not from breast or leukemia cells.

Lysophosphatidic acid (LPA) is present in ascites from patients with ovarian cancer. It stimulates calcium release and growth of ovarian cancer cells both in vitro and in vivo. Recently, we found that LPA levels were significantly elevated in plasma from patients with ovarian cancer and other gynecological cancers. In contrast, LPA levels were not elevated in patients with breast cancer and leukemias. In view of this, we investigated whether gynecological cancer cells could produce LPA. LPA was extracted from the supernatant of cells cultured in vitro and purified by thin layer chromatography. After hydrolysis and transmethylation, the fatty acid derivatives were analyzed by gas chromatography. We found that the phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly stimulated the production of LPA in ovarian and cervical cancer cells. In contrast, a small or negligible amount of LPA was produced in breast cancer and leukemia cells upon PMA stimulation. This cell type specificity correlates with our values of plasma LPA, suggesting that gynecological tumor cells may be an important source of the elevated LPA noted in the plasma of patients with these cancers. The cytosolic PLA2 (cPLA2)/Ca2+-independent PLA2 (iPLA2) inhibitor, AACOCF3, inhibited 75.6% PMA-stimulated LPA secretion in ovarian cancer cells, suggesting a cPLA2/iPLA2 activity was involved in LPA production from ovarian cancer cells.

Breast Neoplasms↗

PubMed1998

Transcriptional regulation of human transcription factor IIB in SMMC-7721 human hepatocellular carcinoma cells by all-trans-retinoic acid and phorbol 12-myristate 13-acetate.

The differential-display reverse transcription/polymerase chain reaction (DDRT-PCR) method was utilised to find genes differentially expressed at the messenger RNA level in SMMC-7721 human hepatocellular carcinoma cells treated and not treated with all-trans-retinoic acid, a differentiation inducer of the cell. Human transcription factor IIB (TFIIB) was discovered to be decreased on the 3rd day after the cells had been treated with retinoic acid and increased by phorbol 12-myristate 13-acetate, which stimulated the proliferation of human hepatocellular carcinoma cells. It was also found that the transcription of TFIIB in SMMC-7721 cell had no relationship to the cell cycle.

Antineoplastic Agents↗

PubMed1998

Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis.

BACKGROUND & AIMS: Cancer of the gallbladder is the number one cause of cancer mortality in Chilean women. Incidence rates for this tumor vary widely on a worldwide basis, being approximately 30 times higher in high-risk than in low-risk populations, suggesting that environmental factors such as infectious microorganisms, carcinogens, and nutrition play a role in its pathogenesis. Because several Helicobacter sp. colonize the livers of animals and induce hepatitis, the aim of this study was to determine whether Helicobacter infection was associated with cholecystitis in humans. METHODS: Bile or resected gallbladder tissue from 46 Chileans with chronic cholecystitis undergoing cholecystectomy were cultured for Helicobacter sp. and subjected to polymerase chain reaction (PCR) analysis using Helicobacter-specific 16S ribosomal RNA primers. RESULTS: Recovery of Helicobacter sp. from frozen specimens was unsuccessful. However, by PCR analysis, 13 of 23 bile samples and 9 of 23 gallbladder tissues were positive for Helicobacter. Eight of the Helicobacter-specific PCR amplicons were sequenced and subjected to phylogenetic analysis. Five sequences represented strains of H. bilis, two strains of "Flexispira rappini" (ATCC 49317), and one strain of H. pullorum. CONCLUSIONS: These data support an association of bile-resistant Helicobacter sp. with gallbladder disease. Further studies are needed to ascertain whether similar Helicobacter sp. play a causative role in the development of gallbladder cancer.

Adult↗

PubMed1998

Cytokine repertoire of epithelial cells lining the human urinary tract.

PURPOSE: To examine the cytokine profile of epithelial cells lining the human urinary tract with the aim of differentiating between the constitutive and disease-related cytokine production in these tissues. MATERIALS AND METHODS: Sections from the renal pelvis, ureter, bladder or urethra were obtained from 22 patients undergoing urinary tract surgery and were stained with monoclonal antibodies to interleukin(IL)-1beta, IL-4, IL-6, IL-8, interferon gamma (IFNgamma) and transforming growth factor beta (TGFbeta). Sections were classified according to the presence or absence of disease in the tissue. RESULTS: Epithelial cells lining the renal pelvis, ureter, bladder or urethra all stained for IL-8 and TGFbeta (100%) in disease-free tissues and sections with cancer or interstitial cystitis (IC). In contrast, staining for IL-1beta, IL-4, IL-6 and IFNgamma varied with the disease state of the patient. Epithelial IL-1beta staining was absent (0%) in sections from healthy bladder, but positive in tissues with IC or cancer-associated pathology (50 to 100%). IL-6 staining was detected in the epithelial layer of several patients with IC or cancer related pathology, but only in cells with non-epithelial morphology and not in disease-free tissues. IFNgamma and IL-4 staining were only observed in patients with IC and only in cells with non-epithelial morphology. CONCLUSIONS: The results show that epithelial cells from all parts of the urinary tract constitutively produce IL-8 and TGFbeta and suggest that the production of other cytokines varies with the disease of the patient. Constitutive cytokine production provides the basis for a rapid host response, in the defense against mucosal attack by microbes or toxic agents.

Adult↗

PubMed1998

Protein kinase C mediates P2U purinergic receptor inhibition of K+ channel in apical membrane of strial marginal cells.

Strial marginal cells (SMC) electrogenically secrete K+ via slowly activating K+ (I[sK]) channels, consisting of I(sK) regulatory and KvLQT1 channel subunits, and the associated short circuit current (I[sc]) is inhibited by agonists of the apical P2U receptor [Liu et al., Audit. Neurosci. 2 (1995) 331-340]. Measurements of relative K+ flux (JK) with a self-referencing K+-selective probe demonstrated a decrease in JK after apical perfusion of 100 microM ATP. On-cell macro patch recordings from the apical membrane of gerbil SMC showed a decrease of the I(sK) channel current (I[IsK]) by 88 +/- 8% during pipette perfusion of 100 microM ATP. The magnitude of the decrease of L(sc) by ATP was diminished in the presence of inhibitors of phospholipase C (PLC) and protein kinase C (PKC), U-73122 and GF109203X. Activation of PKC by phorbol 12-myristate 13-acetate (20 nM) decreased I(IsK) (gerbil: by 62 +/- 10%; rat: by 72 +/- 6%) in perforated-patch whole-cell recordings while the inactive analog, 4alphaPMA, had no effect. By contrast, elevation of cytosolic [Ca2+] by A23187 increased the whole-cell I(IsK). The expression of the isk gene transcript was confirmed and the serine responsible for the species-specific response to PKC was found to be present in the gerbil I(sK) sequence. These data provide evidence consistent with a direct effect of the PKC branch of the PLC pathway on the I(sK) channel of SMC in response to activation of the apical P2U receptor and predict that the secretion of endolymph in the human cochlea may be controlled by PKC in the same way as in our animal model.

Adenosine Triphosphate↗

PubMed1998

Divalent cations inhibit IsK/KvLQT1 channels in excised membrane patches of strial marginal cells.

The IsK/KvLQT1 K+ channel in the apical membrane of strial marginal cells and vestibular dark cells is an essential ion transport pathway for the secretion of K+ into the endolymph of the inner ear. Study of this control point has been impeded by rundown of channel activity upon excision into commonly used cytosolic solutions. This paper describes conditions under which patches of apical membrane of strial marginal cells and vestibular dark cells from gerbil containing this channel can be excised, retaining its characteristic voltage dependence, kinetic properties, ion permeability sequence and pharmacological sensitivity, similar to those found during on-cell and perforated-patch whole cell recordings (Shen et al., Audit. Neurosci. 3 (1997) 215-230). Those excised-patch conditions include removal of Mg2+ from the cytosolic solution and use of a K+-rich pipette electrolyte. The inhibition of channel activity by Mg2+ was found to be a general feature of divalent cations; the channel was also inhibited by Ca2+, Ba2+ and Sr2+. The concentrations causing 50% inhibition of IsK/KvLQT1 channel current were 7 x 10(-5) M, 6 x 10(-6) M, 3 x 10(-4) M and 7 x 10(-5) M, respectively. It was also found that a chemical cross-linking agent, 3,3'-dithio-bis(sulfosuccinimidyl propionate) (DTSSP), which was previously shown to persistently activate IsK/KvLQTI channels expressed in Xenopus oocytes, maintained in excised patches channel activity which retained voltage dependence and pharmacological sensitivity. These data demonstrate that (1) the channel complex is inhibited by Ca2+, Mg2+ and other divalent cations, (2) the activation by Ca2+ observed previously in whole-cell preparations was due to action via other cellular pathways. These findings must be taken into account when considering the action of receptors which alter the cytosolic Ca2+ activity.

Animals↗

PubMed1998

Nuclear factor recognition sites in the gut-specific enhancer region of an Anopheles gambiae trypsin gene.

The major digestive enzyme of Anopheles gambiae is encoded by the trypsin 1 gene. This gene is expressed exclusively in the gut and its mRNA abundance increases after ingestion of a blood meal. Previous experiments with transgenic Drosophila have shown that the enhancer region, from nucleotide -360 bp to -150 bp upstream of the transcription initiation site, is necessary to drive the gut-specific expression of a reporter gene (Skavdis et al., 1996. EMBO J. 15, 344-350). In this study, we defined DNA sequences within this region that are capable of binding nuclear factors from either gut or non-gut tissues. By electrophoretic mobility shift assays, we determined that a gut-specific nuclear factor recognizes and binds to three sites in the enhancer region with a consensus sequence TYCAAGT. Another factor, found in many tissues, recognizes and binds to at least two additional sites with a consensus sequence ACGATA. This study defines for the first time for an insect gut-specific enhancer, specific sequences that interact with nuclear factors.

Animals↗

PubMed1998

Experimental infection in cats with a cagA+ human isolate of Helicobacter pylori.

BACKGROUND: Helicobacter pylori has been cultured from the inflamed gastric mucosa of naturally and experimentally-infected cats. The lesions in the H. pylori-infected cat stomach mimic many of the features seen in human stomachs infected with H. pylori. This study sought to determine whether H. pylori-negative, specific pathogen-free cats with normal gastric mucosa were susceptible to colonization with a human cagA+ strain of H. pylori, and whether gastritis developed after infections. METHODS: Four H. pylori-negative cats treated with cimetidine were orally dosed 3 times at 2-day intervals with 3 ml (1.5 x 108 CFU/ml) of H. pylori. RESULTS: All experimentally-infected cats became persistently colonized as determined by H. pylori isolation from gastric tissue by culture at 12 weeks, and all 4 cats were found positive by PCR during serial gastric biopsies and necropsy at 15 weeks postinoculation. The 2 control cats did not have H. pylori isolated, nor was gastric tissue positive by PCR. The H. pylori isolated from the 4 experimentally-infected cats had RFLP patterns specific for the flaA gene identical to those of the inoculating strain. All 4 H. pylori-infected cats had multifocal gastritis, consisting of lymphoid aggregates plus multiple large lymphoid nodules. In the control cats, one cat had a few focal lymphocytic aggregates in the body submucosa, whereas the second cat had normal gastric mucosa. CONCLUSION: Human cagA+ H. pylori readily colonized the cat stomach and produced a persistent gastritis. The findings demonstrate the utility of the cat to study H. pylori induced pathogenesis.

Animals↗

PubMed1998

Differential gene expression in response to adjunctive recombinant human interleukin-2 immunotherapy in multidrug-resistant tuberculosis patients.

Administration of low-dose recombinant human interleukin 2 (rhuIL-2) in combination with multidrug chemotherapy to patients with multidrug-resistant tuberculosis (MDR TB) induces measurable changes in in vitro immune response parameters which are associated with changes in the clinical and bacteriologic status of the patients. To determine the molecular basis of these changes, we have used semiquantitative reverse transcriptase-initiated PCR (RT-PCR) and differential display technology. During rhuIL-2 treatment of MDR TB patients, decreased levels of gamma interferon (IFN-gamma) mRNA in peripheral blood mononuclear cells (PBMC) relative to baseline levels were observed. However, at the site of a delayed-type hypersensitivity (DTH) response to purified protein derivative of tuberculin (PPD), the expression of cellular IFN-gamma and IL-2 mRNAs was increased during rhuIL-2 therapy. Levels of other cytokine mRNAs were not significantly affected by rhuIL-2 administration. Using differential-display RT-PCR, we identified several genes expressed at the DTH skin test site which were up- or down-regulated during rhuIL-2 treatment. Cytochrome oxidase type I mRNA was increased in response to rhuIL-2 therapy relative to baseline levels, as was heterogeneous nuclear ribonuclear protein G mRNA. CD63, clathrin heavy chain, and beta-adaptin mRNAs, all of which encode proteins associated with the endocytic vacuolar pathway of cells, were also differentially regulated by rhuIL-2 administration. The differential effects of IL-2 were confirmed in vitro by using PBMC obtained from PPD-positive individuals stimulated with Mycobacterium tuberculosis and IL-2. The differential expression of genes may provide a surrogate marker for leukocyte activation at a mycobacterial antigen-specific response site and for the development of an enhanced antimicrobial response which may result in improved outcomes in MDR TB patients.

Adult↗

PubMed1998

Comparison of methods of identifying Helicobacter hepaticus in B6C3F1 mice used in a carcinogenesis bioassay.

In a long-term rodent bioassay evaluating the carcinogenicity of triethanolamine, there was equivocal evidence of carcinogenic activity in male B6C3F1 mice, based on a marginal increase in the number of hepatocellular adenomas and hepatoblastomas. Interpretation was complicated by the presence of Helicobacter hepaticus in selected silver-stained liver sections which also had histological evidence of karyomegaly and oval cell hyperplasia. An increase in numbers of liver tumors, as evidence of carcinogenic activity, was also noted in female mice. However, H. hepaticus was not considered a complicating factor, because the livers of the female mice did not have histological features compatible with H. hepaticus infection. A retrospective analysis of 51 liver tissue samples from the original carcinogenicity study was conducted to determine the incidence of H. hepaticus infection and to evaluate different diagnostic approaches for assessing the presence of H. hepaticus in livers lacking characteristic lesions. In an initial evaluation of seven mice with liver tumors, argyrophilic bacteria resembling H. hepaticus were observed in liver sections, associated with characteristic liver lesions of hepatocytic karyomegaly and oval cell hyperplasia. Frozen liver tissue was available from four of these mice; all were confirmed to be infected with H. hepaticus by culture and PCR. In a larger subsequent analysis using frozen liver tissues from 44 mice without characteristic hepatic lesions, H. hepaticus-specific DNA was amplified from the livers of 21 of 44 of the mice (47%), compared to 14 of 44 of the mice (32%) having H. hepaticus cultured from their frozen liver tumors. The results of H. hepaticus culture and H. hepaticus-specific PCR concurred (i.e., both positive and negative results) in 84% of the cases. Microscopic detection of immunofluorescence-labeled or silver-stained bacteria in liver sections was relatively insensitive compared to either culture or PCR detection. This study confirms the widespread prevalence of H. hepaticus in mice, its potential to confound experimental results, and the need to include diagnostic testing for H. hepaticus in a murine health monitoring program.

Animals↗

PubMed1998

Development of a PCR-restriction fragment length polymorphism assay using the nucleotide sequence of the Helicobacter hepaticus urease structural genes ureAB.

Infection with Helicobacter hepaticus causes chronic active hepatitis in certain strains of mice and is associated with hepatocellular carcinoma in A/JCr mice. Like the gastric helicobacters, H. pylori and H. mustelae, H. hepaticus possesses a high level of urease activity. However, the H. hepaticus urease structural gene sequences have not been previously determined, and the role of the urease enzyme in colonization and in pathogenesis is not known. PCR was used to amplify a portion of the urease structural genes from H. hepaticus genomic DNA. Amplified DNA fragments were cloned, and the nucleotide sequence was determined. The deduced amino acid sequence of the partial H. hepaticus ureA gene product was found to exhibit 60% identity and 75% similarity to the predicted H. pylori UreA. The deduced amino acid sequence of a partial H. hepaticus ureB gene product exhibited 75% identity and 87% similarity to the predicted H. pylori UreB. Diversity among H. hepaticus isolates was evaluated by means of a restriction fragment length polymorphism (RFLP) assay. The 1.6-kb fragments within the ureAB open reading frames, amplified from 11 independent isolates, were digested with the restriction endonuclease HhaI. Three distinct RFLP patterns were observed. Identical RFLP profiles were noted in sequential isolates of one strain of H. hepaticus during an 18 month in vivo colonization study, suggesting that the urease genes of H. hepaticus are stable. The urease genes among H. hepaticus strains were also well conserved, showing 98.8 to 99% nucleotide sequence identity among three isolates analyzed. These findings indicate that H. hepaticus has urease structural genes which are homologous to those of the gastric Helicobacter species and that these gene sequences can be used in a PCR and RFLP assay for diagnosis of this important murine pathogen.

Amino Acid Sequence↗

PubMed1998

Inflammatory large bowel disease in immunodeficient rats naturally and experimentally infected with Helicobacter bilis.

Proliferative and ulcerative typhlitis, colitis, and proctitis were found incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within the crypts of the large intestine, modified Steiner's silver stain revealed spiral organisms that were identified by culture, polymerase chain reaction, and sequencing to be Helicobacter bilis. The large bowel disease was reproduced in H. bilis-free male athymic nude rats that were injected intraperitoneally with a culture of H. bilis from the affected colony. The organism was isolated from the feces and cecum of the experimentally infected rats. H. bilis should be considered a potential pathogen in immunocompromised rats. The infection in immunocompromised rats may serve as an animal model for inflammatory large bowel disease.

Animals↗

PubMed1998

[One stage repair and reconstruction for severe deep burns with compound tissue defects of upper limb].

In order to solve the difficult problems of repair and reconstruction for severe deep burns with compound tissue defects of upper limb, 26 cases were treated with transplantation of compound tissue flap, vascularized by anastomosis of blood vessel or by vascular pedicle. Several kinds of reparative and reconstructive procedure could be performed simultaneously. Not only the tissue defect was repaired, but also the upper limb function was reconstructed in one stage operation. Owing to the presence of abundant vascular supply from the vascularized compound tissue and primarily closing the wounds, the anti-infection potency was high, then it was suitable for such conditions as fresh severe deep burn with infection and compound tissue defects. As a result, this technique provided the best chance to save upper limb from amputation. The duration required for treatment could be markedly shortened. All the cases successed. The long-term functional recovery was satisfactory. This method provided the possibility to solve effectively the difficult problem dealing with the severe deep burns with compound tissue defects of upper limb.

Adolescent↗

PubMed1998

[Basic fibroblast growth factor (bFGF) and wound healing: a multi-centers and controlled clinical trial in 1024 cases].

UNLABELLED: To evaluate the effects of bFGF on wound healing and the side-effects of bFGF, a multi-centers and controlled clinical trial were carried out in 32 hospitals in China. One thousand and twenty-four cases with acute wounds such as burn, donor site or operative wound and chronic wounds such as bed sore, draining sinus, ulcer were treated with bFGF. Another 826 cases with the similar wounds were used as control. The results showed: 1. The duration of wound healing was shorted 3-4 days in trial group when compared with the contorl; 2. The successful rates from bFGF on promoting the wound healing for burns, operative wounds and chronic dermal ulcers was 95.2%, 96.5% and 93.5%, respectively; 3. No adverse reaction was found. CONCLUSION: 1. bEGF can make the "silent" reparative cells dividing and proliferating. 2. bFGF can improve the quality and the velocity of wound healing.

Administration, Topical↗