Biomedical subjects

P C Stein

Publications and source records attributed to P C Stein.

At least 19 recordsLinked to original sources

PubMed2001

Biphasic behavior of the high-spin-->low-spin relaxation of [Fe(btpa)](PF6)2 in solution (btpa = N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine).

The light-induced high-spin-->low-spin relaxation for the Fe(II) spin-crossover compounds [Fe(btpa)](PF6)2 and [Fe(b(bdpa))](PF6)2 in solution, where btpa is the potentially octadentate ligand N,N,N',N'-tetrakis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'-bipyridine and b(bdpa) is the analogous hexadentate ligand N,N'-bis(benzyl)-N,N'-bis(2-pyridylmethyl)-6,6'-bis(aminomethyl)-2,2'- bipyridine, respectively, has been studied by temperature-dependent laser flash photolysis. [Fe(b(bdpa))](PF6)2 shows single-exponential 5T2-->1A1 relaxation kinetics, whereas [Fe(btpa)](PF6)2 exhibits solvent-independent biphasic relaxation kinetics. The fast process of [Fe(btpa)](PF6)2 with a rate constant, kHL, of 2.5 x 10(7) s-1 at 295 K and an activation energy, Ea, of 1294(26) cm-1 in methanol can be assigned to the 5T2-->1A1 relaxation as well. The slow process with a kHL(295 K) of 3.7 x 10(5) s-1 and a Ea of 2297(32) cm-1 in methanol--which is the slowest light-induced relaxation process observed so far for an Fe(II) spin-crossover complex in solution--is assigned to a coupling of the 5T2-->1A1 relaxation process to a geometrical rearrangement within the pendent pyridyl arms.

Journal Article↗

PubMed2001

Estrogenic regulation of HSP90 kD synthesis in rat urinary bladder.

The role of heat shock protein (HSP90 kD) has been investigated in regard to its association with steroid receptors. HSP90 kD may play a role in steroid receptor stabilization and activation. Oophorectomized Sprague-Dawley rats (n = 25) were placed into five groups and injected subcutaneously with 30 microg beta-estradiol 17-benzoate in sesame oil, with one group injected with carrier oil (control). After estrogen administration, the rats were killed, and their bladders removed for immunostaining, immunoblotting and enzyme-linked immunosorbent assay (ELISA). Immunoblot analysis demonstrated a 90-kD band in bladder homogenates, even in the absence of estrogen. However, the bands were more intense 12 and 24 h after administering estrogen. ELISA showed significant differences in HSP90 kD synthesis as early as 6 h compared to controls (P< 0.05). After 48 h the estrogen-treated rats and controls were identical. The above results were confirmed by immunostaining for HSP90 kD. HSP90 kD synthesis in the rat urinary bladder is under estrogenic regulation. These findings may be relevant in the etiology and pathobiology of interstitial cystitis and menopausal voiding dysfunctions since the bladder is enriched with estrogenic receptors and is under estrogenic influence.

Animals↗

PubMed2000

Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis.

PURPOSE: Tamm-Horsfall protein (THP) is a ubiquitous urinary protein with essentially no known function. We propose that THP is a cytoprotective agent that protects the urothelium from cationic species. To test this hypothesis we isolated THP from normal and interstitial cystitis urine to see if it could protect cultured cells from damage induced by the polyamine, protamine sulfate (PS). METHODS: Tamm-Horsfall protein was extracted from the urine of interstitial cystitis (IC) patients (N=28) and normal volunteers (N=5). Urothelial target cells (T24) were radiolabeled with 51Cr and then exposed to PS (0-1.0 mg/mL) for either 1.5 or 20 h. The resulting cytotoxicity data (dose-response curves) were then compared with the data obtained when PS was preincubated with 0-0.5 mg/mL of THP (IC vs normal), the semisynthetic polysaccharide, pentosan polysulfate (Elmiron), or human serum albumin. RESULTS: Toxicity of PS was significantly reduced by incubation with THP (or Elmiron) prior to evaluation by the chromium release assay, but not reduced by incubating with another protein, albumin. Tamm-Horsfall protein from IC patients' urine was less protective than an equal quantity of THP from normal urine. CONCLUSIONS: These experiments suggest that THP has an important role in bladder mucosal defense mechanisms, protecting the bladder surface from injury. Inability of THP to prevent cytotoxic damage by urinary polyamine or other urinary toxins (cationic species) may be relevant in the etiology of interstitial cystitis, as putative urinary toxic components have been described in the urine of some patients.

Adjuvants, Immunologic↗

PubMed2000

Cyto-injury factors in urine: a possible mechanism for the development of interstitial cystitis.

PURPOSE: In most of our patients with interstitial cystitis (IC), the disease is associated with an increased urothelial permeability whose cause has not been identified. We postulate that both normal urine and the urine of IC patients contains factors capable of injuring the mucosa and causing an increased permeability that would allow urine components to leak into the bladder muscle. To test this hypothesis, we examined fractions of normal urine for toxic effects on bladder smooth muscle and epithelial cells in vitro. In the same in vitro system, we measured the effects of Tamm-Horsfall protein (THP), a normal urinary glycoprotein that may be a scavenger of injurious agents capable of "detoxifying" normal metabolic products. MATERIALS AND METHODS: Human urothelial cells (T24) and rabbit bladder smooth muscle cells were incubated overnight with various fractions prepared from healthy volunteers' urine. The urine fractions of molecular weights >100 Da were incubated overnight with either urothelial or smooth muscle target cells after no treatment or after heating to 56C, preincubation with THP, exposure to heparin, or elution from heparin. Cytotoxicity was determined for each group using a neutral red uptake assay. RESULTS: Urine fractions of molecular weight 500 to 1000 Da were cytotoxic to smooth muscle cells (39%) and urothelial cells (50%). Cytotoxicity levels for THP-treated fractions were significantly lower than those for untreated fractions in both urothelial cells (7% versus 89%, p <0. 001) and smooth muscle cells (8% versus 70%, p <0.01). Fractions exposed to heparin were less cytotoxic to smooth muscle cells (20%) than were untreated fractions (27%). Fractions eluted from heparin were also cytotoxic to urothelial cells (42%). CONCLUSIONS: Normal human urine contains heat labile, cationic components of low molecular weight that bind to heparin. These components, when separated from the bulk of the urinary wastes, are cytotoxic to urothelial cells as well as underlying smooth muscle cells, indicating their potential for causing bladder mucosal injury. The cytotoxic activity can be blocked by the presence of THP. This urinary cytoprotective activity of THP may play an important but unrecognized role in the development of IC.

Adult↗

PubMed1999

Elevated urinary norepinephrine in interstitial cystitis.

OBJECTIVES: To measure urinary catecholamines and determine the extent to which they may be elevated in urine from patients with interstitial cystitis (IC). METHODS: Random urine samples from patients with IC (n = 111) and urine from normal volunteers (n = 92) were acidified on collection (voided and catheterized specimens) and assayed for catecholamine (norepinephrine or normetanephrine) by enzyme-linked immunosorbent assay. Creatinine levels in these urine samples were also measured. RESULTS: Analysis of the data indicated that patients with IC had a higher urinary level of the neurotransmitter norepinephrine compared with the measured levels in the urine of normal volunteers (89.1 +/- 58.3 versus 54.9 +/- 37.1 microg/g creatinine, P <0.05). The metabolite normetanephrine was similar in the urine samples from these two groups. Urine from patients with bladder outlet obstruction (n = 11) did not have elevated amounts of urinary norepinephrine. The norepinephrine levels were not statistically different in the urine samples from patients with symptomatic and asymptomatic IC. The elevated urinary levels in patients with IC did not decrease after treatment with sodium pentosanpolysulfate (Elmiron), heparinoids, dimethyl sulfoxide, or combinations of these during 1 to 15 months of treatment. CONCLUSIONS: Norepinephrine was found to be elevated in the urine from patients with IC compared with urine from normal controls. This would be consistent with increased sympathetic (adrenergic) activity from the bladders of patients with IC or possibly from increased adrenal activity, since stress is associated with symptom increase in some patients with IC. Norepinephrine levels did not decrease with treatment nor did they differ between symptomatic and asymptomatic patients at the time of urine collection.

Adult↗

PubMed1998

Elevated stress protein in transitional cells exposed to urine from interstitial cystitis patients.

BACKGROUND: It has been hypothesized that urine from interstitial cystitis (IC) patients may contain one or more toxic factors not present in "normal" urine. Bladder tissues exposed to these toxic factors could have elevated stress proteins. If this assumption is correct, stress protein levels could be a useful marker for identifying patients at risk for developing this syndrome. METHODS: To experimentally investigate this possibility, a sensitive assay (ELISA) was used to measure levels of the 72 kDa stress protein in urothelial target cells after in vitro exposure to urine from IC patients. RESULTS: We observed a modest 12% increase in 72 kDa stress protein in cells treated with urine from IC patients compared to cells exposed to normal urine (1.12 compared to 0.99 ng/microg extracted protein; P < 0.05). In addition, it was possible to demonstrate the 72 kDa stress protein in histologic sections obtained from mucosal biopsies of IC patients. Stress protein was located primarily in the surface urothelial cells of the mucosa. CONCLUSIONS: These results seem to indicate that stress protein could play an important protective role at this particular site. They further suggest that IC urine is more toxic than normal urine and, in contact with underlying urothelial and deeper bladder tissue, may upregulate genes involved in stress protein responses. This may be an important concept in the etiology of IC.

Biomarkers↗

PubMed1997

Dynamic bis-intercalation of a homodimeric thiazole orange dye in DNA: evidence of intercalator creeping.

We have used one and two dimensional exchange 1H NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis- 4-(3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinol inium tetraiodide (TOTO), to double stranded DNA (dsDNA). The double stranded oligonucleotides used were d-(CGCTAGCG)2 (1) and d(CGCTAGCTAGCG)2 (2). TOTO binds preferentially to the (5'-CTAG-3')2 sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with 2 in ratios dependent on the relative amount of TOTO and the oligonucleotide in the sample. The dynamic exchange between preferential binding sites in the case of a 2:1 1-TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 2-TOTO complex an intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results demonstrate the ability of TOTO to migrate along a dsDNA strand in an intramolecular exchange process. The migration process ("creeping") along the DNA strand is 6 times faster than the rate of intermolecular exchange between sites in two different oligonucleotides.

Benzothiazoles↗

PubMed1996

Electrophysiologic monitoring of the effects of soluble virulence factors produced by Escherichia coli infection in urine.

OBJECTIVES: The presence of soluble virulence factors in urine infected by Escherichia coli has been postulated by recent studies in a rabbit bladder model. These substances may enhance bacterial adherence by damaging the glycosaminoglycan (GAG) layer that normally blocks both bacterial adherence and diffusion of solutes to the level of the epithelial membrane. We evaluated the effects of E. coli-infected urine on New Zealand white rabbit bladder mucosal permeability by measuring conductance (g) and current (I) and then calculating resistance (R) using the formula R = I divided by g. METHODS: Forty-five rabbit bladders were prepared and mounted in Ussing chambers. The group was divided equally into three smaller cohorts (n = 15). The first cohort (NL) was exposed to uninfected sterile-filtered urine, the second cohort (PS) was a positive control exposed to uninfected sterile-filtered urine containing protamine sulfate, and the final cohort (INFX) was exposed to supernatants of E. coli-infected (more than 10(7) colony-forming units) sterile-filtered urine. The average time of exposure was 160 minutes, and the previously mentioned electrophysiologic parameters were measured and recorded. RESULTS: The results of the PS group showed statistically significant differences in conductance, current, and resistance compared with the NL group. The decline in resistance accompanied by elevation in both current and conductance was an indirect indication that the GAG layer was functionally disturbed with a secondary increase in mucosal permeability. In a similar fashion, the INFX group also showed a statistically significant rise in conductance as well as a decline in resistance. CONCLUSIONS: These data support the concept that E. coli-infected urine contains soluble factors that can damage the GAG layer. Although these substances appear to be less potent than quaternary or polyamines such as protamine sulfate, their mechanism of action appears similar and may enhance bacterial virulence.

Animals↗

PubMed1996

Bladder injury model induced in rats by exposure to protamine sulfate followed by bacterial endotoxin.

PURPOSE: A bladder injury model was developed using protamine sulfate (PS) and endotoxin lipopolysaccharide (LPS) administered intravesically to female Sprague-Dawley rats. MATERIALS AND METHODS: Experimental and control animals were catheterized and intravesically exposed to PS-LPS, PS, LPS, or phosphate buffered saline. After 4, 24 or 72 hours, rats were sacrificed. Urines and bladder tissues were then obtained. Bladder mucosal permeability was evaluated by measuring 14C-urea uptake 24 hours after injury. Repeated instillations of PS/LPS were also made in another group of rats over a period of 5 weeks to attempt to establish a more serious mucosal injury, possibly reflected by altered staining of the collagen IV component of the urinary basement membrane (UBM). RESULTS: Histological examination of the tissues indicated a maximal inflammatory response in the mucosa 4 hours after instillation of PS/LPS. Neutrophils and macrophages in close proximity to the UBM and intraepithelially could be demonstrated. Bladder permeability was significantly altered (26.9% 14C-urea uptake) in rats assayed 24 hours after the PS/LPS treatment, but not after exposure to PS or LPS alone (11.9 and 17.5%, respectively). Protease activity detected in urines from experimental, but not control, animals coincided with the appearance of inflammatory cells in the lamina propria. Inflammatory injury did not appear to alter the collagen IV staining of the UBM. CONCLUSIONS: This rat bladder injury model is useful for examining controversial issues regarding bladder wall structure-function alterations induced by inflammation and possibly important in the pathobiological mechanisms involved in some patients with interstitial cystitis.

Animals↗

PubMed1995

A comparison of the hairpin stability of the palindromic d(CGCG(A/T)4CGCG) oligonucleotides.

The palindromic deoxyribonucleotides 5'-CGCGA-TATCGCG-3' and 5'-CGCGTTAACGCG-3' have been characterized by 1H NMR spectroscopy. The NMR data identified both B-DNA duplex conformations and hairpin conformations, the latter with loop regions consisting of the four central nucleotides. The resonances of the various conformations were assigned by use of two-dimensional NMR methods. The relative stability of the various conformations was investigated as a function of temperature, ionic strength and nucleotide concentration. The duplexes were found to be stabilized at high ionic strength and at low temperature, while the hairpins were stabilized at low ionic strength and at medium temperature. The thermodynamics of the duplex-hairpin and the hairpin-random coil transitions were examined, and compared to the other two oligonucleotide in the palindromic d(CGCG(A/T)4CGCG) oligonucleotide family. The relative stabilities of the duplex conformations with respect to the random coil conformations are similar for the d(CGCGAATTCGCG), d(CGCGATATCGCG) and d(CGCGTATACGCG) oligonucleotides. The duplex conformation of d(CGCGTTAACGCG) is less stable. The hairpin of d(CGCGTTAACGCG) seems also to be less stable relative to the random coil conformation than in the case of the other oligonucleotides at an equal oligonucleotide concentration. A cruciform intermediate between the duplex and hairpin conformations is suggested to explain some discrepancies observed in this work in case of the d(CGCGTTAACGCG) oligonucleotide. This is similar to what has been reported for the d(CGCGTATACGCG) oligonucleotide.

DNA↗

PubMed1995

Intestinal de-epithelialization and augmentation cystoplasty: an animal model.

OBJECTIVES: An animal model of augmentation cystoplasty was developed in New Zealand rabbits to study the effects of intestinal de-epithelialization on subsequent re-epithelialization by bladder urothelium. METHODS: Twenty-four rabbits underwent augmentation cystoplasty using intestinal segments that were either treated with protamine sulfate and urea solution or else anastomosed with an intact epithelium. Half of the rabbits receiving the de-epithelialized intestinal segments were subjected to glycosaminoglycan replacement therapy by administration of intravesical heparin. Experimental and control rabbits were sacrificed at 1-, 2-, and 3-month intervals. RESULTS: Histologic examination of the augmented sections showed small areas of urothelium growing over the intestinal epithelium (approximately 15%). The heparin-treated group demonstrated the greatest amount of re-epithelialization. There was no obvious histologic difference in the amount of collagen present in the augmented tissues in any of the experimental groups. CONCLUSIONS: In a preliminary study, New Zealand rabbits appear to be satisfactory as an experimental animal for studying the augmentation cystoplasty procedure and for the development of therapeutic interventions for enhancing epithelial growth. Protamine and urea will de-epithelialize the bowel and heparin may promote epithelialization of augmented intestinal segment by transitional epithelium.

Anastomosis, Surgical↗

PubMed1995

Characterization of microbial presence at the surface of silicone mammary implants.

The purpose of this project was to examine the incidence of microbial presence on the surface of mammary implants and its correlation with clinical presentation. The significance of microbial presence without signs of overt infection is questioned. Several issues are raised, including whether the presence of micro-organisms may immunize the host, trigger autoimmune reactions, or locally change the course of healing (resulting in capsular contracture). A total of 150 explanted silicone mammary implants from 87 patients were cultured. Cultures of 81 devices were positive (54%); the predominant isolate was Staphylococcus epidermidis (found on 68 implants, or 84%). Bacteria were detected on 76% (62 of 82) of implants surrounded by contracted capsules and on 28% (19 of 68) of those without capsular contracture (p < 0.05). Among 40 patients (46%) who had no general health problems, 11 (28%) had positive cultures of explanted devices (15 of 62 explants, or 24%). In the remaining 47 patients (54%) who complained of myalgia (77%), arthralgia (68%), chronic fatigue (38%), skin rashes (21%), cognitive problems (19%), dry mucosal membranes (19%), episodes of low-grade fever (17%), and hair loss (13%), 38 (81%) had positive cultures (66 of 88 explants, or 75%) (p < 0.05). The hypothesis that capsular contracture or problems that might be related to chronic infection and immunization are associated with subclinical infection is supported by this study.

Adult↗

PubMed1995

Selective type IV collagen defects in the urothelial basement membrane in interstitial cystitis.

PURPOSE: The study sought to identify changes in the urothelial basement membrane (UBM) associated with interstitial cystitis (IC). MATERIALS AND METHODS: Immunohistochemical assessment of bladder biopsies from IC patients and controls was compared with clinical and histologic findings. RESULTS: Selective decreases or loss of type IV collagen staining, but not laminin, were found in the UBM of 5 of 11 IC patients with no change in type IV collagen staining of other bladder wall sites. CONCLUSIONS: The loss of type IV collagen may represent a primary or secondary event and could alter the UBM's role in permeability, thereby contributing to the pathogenesis of IC in the subset of IC patients exhibiting this change.

Adult↗

PubMed1995

Production of soluble virulence factor by Escherichia coli.

Experimental evidence suggests that adherence is a prerequisite for bacterial infection. We demonstrated that transitional cells at the surface of the bladder are coated with glycosaminoglycans (proteoglycans and mucus) whose presence efficiently decreases bacterial adherence to the mucosa. Exposure of mucus to protamine sulfate, a quaternary amine (known to form salts with glycosaminoglycans and inactivate them) significantly increases the bacterial adherence to the bladder. Investigators have primarily focused on bacterial surface factors (that is pili or fimbriae, glycocalix) in relation to the ability to adhere. We explored the hypothesis that Escherichia coli produces a soluble virulence factor that increases the infection rate in rabbits by promoting bacterial adherence to the bladder mucosa. In addition, it was proposed that this factor is a quaternary amine similar to protamine. For these studies an in vivo bacterial infection assay (which we described previously in rabbits) was used to examine E. coli metabolic products (soluble virulence factor) that could promote bacterial persistence in the bladder by perturbing mucus (glycosaminoglycans), and promote bacterial adherence and virulence. E. coli was grown in human urine and a bacterial-free supernatant was collected. Rabbit bladders were then exposed to either this supernatant or to the same human urine that was not infected with E. coli. Results show a significantly higher bacterial persistence (bacterial count) in bladders pretreated with urine containing the E. coli supernatants compared to controls pretreated with uninfected urine (p = 0.03). The molecular weight of the putative soluble virulence factor is less than 3.5 kD. (p = 0.056) based on dialysis studies and binds to heparin agarose affinity chromatography matrix, suggesting that it is cationic and capable of adhering to the highly anionic bladder mucus (glycosaminoglycans).

Animals↗

PubMed1994

Abnormal sensitivity to intravesical potassium in interstitial cystitis and radiation cystitis.

The urgency-frequency syndrome (UFS) (non-bacterial cystitis, interstitial cystitis) may well represent a heterogenous group with several etiologies. This study was based on the hypothesis that one subset of UFS patients has a leaky (to solutes) epithelium and cations such as potassium could thereby diffuse subepithelially and provoke symptoms. It was also hypothesized that normal impermeable transitional epithelium would not allow cations to diffuse across the cells during the K+ provocation test and no symptoms would be experienced. If the epithelium was permeable ("leaky"), diffusion would occur and provoke symptoms. Water or 0.4 M KCl was placed intravesically into normal volunteers and interstitial cystitis (IC) patients. Water did not provoke symptoms in either group but KCl provoked 4.5% of normals and 70% of IC patients. Differences were significant (P < 0.0001). This test provides a valuable diagnostic tool for UFS and a valuable research tool to separate epithelial permeability problems from other subsets of patients. A third group, consisting of 11 IC patients in remission on heparinoid therapy, was also tested and only 18% were provoked by KCl. Four patients with radiation cystitis were also examined and all four (100%) were provoked by the potassium.

Administration, Intravesical↗

PubMed1994

Proteoglycan core protein syndecan in bladder biopsies.

The etiology of interstitial cystitis (IC) may be related to a dysfunctional epithelium caused by an abnormal permeability barrier. The presence of deleterious urinary substances (quaternary amines) that alter an otherwise normal epithelium may also be contributory. IC disease could reflect an inability of the bladder to repair its protective surface-coat material (glycosaminoglycans and proteoglycans), which is constantly exposed to a toxic urine environment. Bladder biopsy tissue from IC patients and derived explant cells were investigated to determine if mRNA for a proteoglycan core protein could be extracted and evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Syndecan was chosen for this investigation because the available sequence information permitted PCR primers to be synthesized. The results indicated that biopsy tissue and explant cells could be utilized for the isolation of syndecan core protein mRNA. This proteoglycan was also demonstrated in mouse bladders by immunostaining and immunoblotting (but not in human tissues) using a syndecan-specific monoclonal antibody (281-2). Quantitative differences in IC tissues versus normal bladder tissue with respect to gene expression for this proteoglycan core protein can now be determined.

Animals↗

PubMed1994

A new method for cytodestruction of bladder epithelium using protamine sulfate and urea.

Bladder epithelium relies primarily on the presence of a surface glycosaminoglycan (GAG) layer and the structural integrity of cell-cell contact to maintain impermeability to toxic urinary wastes. Previous clinical studies evaluating bladder permeability characteristics in interstitial cystitis patients had indicated that epithelial desquamation occurs after treatment with protamine sulfate (PS) followed by hypertonic urea. The following study was performed using rabbits to further investigate this finding. The urinary bladder was evaluated for optimal treatment conditions for epithelial removal. Protamine sulfate (1 to 10 mg./ml.) and urea (100 to 200 gm./ml.) were instilled into the bladder at volumes ranging from 5 to 60 ml. to that required for near maximum distention. After incubation at room temperature for 15 minutes, the bladders were fixed and evaluated histologically for epithelial removal. The maximum epithelial removal occurred when the bladders were distended, and when PS concentration was 5 to 10 mg./ml. and urea at 200 gm./l. There was greater epithelium removal after repeated treatments. Epithelial cells that were removed were not viable based on Trypan blue staining. There was no significant increase of C14 labeled urea in the plasma after 15 minutes. Rabbits that were followed for 6 weeks after treatment did not show any histological evidence of increased collagen deposition and/or fibrosis. This procedure may have important clinical value since it may remove sufficient bladder epithelium in patients with transitional cell carcinoma to have therapeutic benefit. This offers a realistic option for selective, nontoxic destruction of bladder epithelium.

Administration, Intravesical↗

PubMed1994

Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo.

We have previously demonstrated that the quaternary amine, protamine sulfate (PS), is bactericidal against Staphylococcus epidermidis. In an attempt to decrease genitourinary prosthesis infection rates, we examined the ability of PS as a wound irrigant to inhibit Staphylococcus epidermidis viability. Eighty-seven Sprague-Dawley rats were studied by implanting a sterile silicone pellet in their dorsum. The pellet was inoculated with Staphylococcus epidermidis and the rats were divided into four groups based on the wound irrigant employed after inoculation: (1) control (sterile water) (2) vancomycin; (3) PS; (4) vancomycin + PS. All rats received perioperative and daily intramuscular vancomycin, and the pellets were explanted on postoperative day 28 and cultured. The infection rates were: (1) control 77%, (2) vancomycin 50%, (3) protamine sulfate 67%, and (4) protamine sulfate and vancomycin 19%. The differences between (2) vancomycin versus (4) vancomycin + PS and (3) PS versus (4) vancomycin + PS were significant (p = 0.05 and p < 0.005). The data suggest that PS potentiates vancomycin as a wound irrigant in prosthesis implantation.

Animals↗