Subcutaneous Silicone Research Articles

Microgrooved silicone subcutaneous implants in guinea pigs

Cell–substratum interactions are of fundamental importance for the reaction of body tissues to surgically implanted foreign materials. In our study we investigated the influence of 2 μm wide microgrooves, with various depths (0.5–6 μm), on capsule formation around subcutaneous silicone implants, in an animal experiment. Silicone sheets with microtexture were glued around silicone tubes. These implants were placed subcutaneously in eight guinea pigs for 10 weeks. The implanted tubes were removed including all surrounding tissues, and processed for light microscopy and subsequent histomorphometrical evaluation. All removed implants were surrounded by a thin fibrous capsule, and it was observed that this capsule was separated from the implants by a thin, single layer of mono- and multinucleated phagocytotic cells. In histomorphometry no significant differences were seen in relation to the reaction towards the various textures. We conclude that microtextures do not have an effect on the morphological characteristics of capsule formation around silicone implants in soft tissue.

Improved nerve regeneration with neutralization of transforming growth factor-beta1.

Recovery of injured peripheral nerves depends on a balance between Schwann cell regeneration and scar formation. Transforming growth factor-beta1 (TGF-beta1) has been implicated as a humoral stimulus in scar formation. The neutralization of TGF-beta1 has been beneficial in the reduction of fibrosis. This study was to identify the presence of TGF-beta1 in regenerating peripheral nerve and to measure motor nerve regeneration by the neutralization of TGF-beta1 in neural wounds. A randomized study of rat sciatic nerve regeneration. Sciatic nerve axotomy was performed, followed by serial immunohistochemical staining by anti-TGF-beta1 at 12 to 216 hours (n = 5). Two groups (n = 10) with sciatic axotomy and epineural repair were treated with a 7-day perineural administration of neutralizing antibody of TGF-beta1 or saline carrier via subcutaneous silicone infusion port. A control group (n = 10) without axotomy with anti-TGF-beta1 administration was established. At 12 weeks the compound muscle action potential amplitude (CMAP) and the muscle twitch strength generated by the gastrocnemiussoleus muscle complex were measured. TGF-beta1 was qualitatively present with maximal concentration by 72 to 144 hours. CMAP amplitude in the anti-TGF-beta1/axotomy group was 49.6% of the control and the axotomy/saline group was 31% of the control. Muscle twitch strength was 74% and 46.5%, respectively. These differences were statistically significant, P = .05. The presence of TGF-beta1 at regenerating nerve sites was confirmed. The benefit of neutralization of transforming growth factor on CMAP and muscle twitch strength was shown. These results suggest improved regeneration at nerve injury sites with neutralization of TGF-beta1.

Local administration of neurotrophic growth factor in subcutaneous silicon chambers enhances the regeneration of the sensory component of the rat sciatic nerve.

An experimental model for local administration of neurotrophic growth factor (NGF) in peripheral nerve lesions is tested. The model consists of a subcutaneous reservoir connected to the sciatic nerve neurorrhaphy. The right sciatic nerves were exposed, severed, and repaired at a level 1.5 cm proximal to their trifurcation. Then, a dome-shaped silicone reservoir connected to the proximal end of a silicone tube was placed subcutaneously in the dorsum of the experimental animal. The distal end of the connecting tube was located in the nerve neurorrhaphy. Two experimental groups were made: Group A (n = 90) received daily doses of a solution containing NGF-7S during the first 4 weeks after surgery and a single weekly dose thereafter. Within this group, three subgroups of 30 rats each were made: A-4 sacrificed 4 weeks after surgery, A-8 sacrificed after 8 weeks, and A-12 after 12 weeks. Group B (n = 90) received the same vehicle solution without NGF under the same schedule and volume as in Group A. Three subgroups were also made as in Group A depending on the survival period. In order to locate the neurons in the dorsal root ganglia, the retrograde tracer horseradish peroxidase was administered at the proximal stump of the sciatic nerve (tibialis branch), which was severed 1 cm distal to the sciatic trifurcation. In respect of the nonoperated side, the percentage between the number of dorsal root ganglia neurons in the NGF-treated group was significantly higher than in the control group (P < 0.001). These results demonstrate that percutaneous administration of multiple doses of NGF in this model enhances sensory nerve regeneration after sciatic lesions evaluated by horseradish peroxidase labeling of dorsal root ganglia neurons.

Local administration of neurotrophic growth factor in subcutaneous silicon chambers enhances the regeneration of the sensory component of the rat sciatic nerve

Local administration of neurotrophic growth factor in subcutaneous silicon chambers enhances the regeneration of the sensory component of the rat sciatic nerve

Duration of ovulation suppression with subcutaneous silicone implants containing norgestomet in Bos indicus heifers and cows.

The aim of this study is to determine the duration of suppressing oestrus or ovulation in Bos indicus heifers and cows using norgestomet (N) incorporated into a silicone implant. Twelve heifers and 18 cows undergoing oestrous cycles were allocated to one of two treatment groups (6 heifers and 9 cows per group). Animals were treated with a single subcutaneous (s.c.) silicone implant containing 3 mg of N or two identical silicone implants (6 mg of N in two silicone implants) on day 0 of the study. An analogue of prostaglandin F2-alpha was administered intramuscularly, to all animals on days 0 and 6 to induce regression of corpora lutea. Implants were removed from all animals on day 21. Animals were observed for signs of behavioural oestrus while implants were in situ and for 6 d following implant removal. Blood samples were collected on alternate days from day 0 to 20 and again on day 21 and analysed for plasma progesterone (P4). Transrectal ultrasonography was performed on days 0, 6, 10, 14, 18, 21, 24, 26,27, and along with concentration of P4 in plasma was used to confirm ovulation during the treatment period. The cumulative percentages of animals ovulating during the 21 days implants were in situ were 6.7% (3 mg of N in one silicone implant) and 0% (6 mg of N in two silicone implants)Intervals from implant removal to oestrus (mean +/- S.E.M.) did not differ significantly among animals treated with either 3 or 6 mg of N in silicone implants (46.8 +/- 7.0 vs. 55.4 +/- 7.1 h, P = 0.398). Variances in interval from implant removal to oestrus among animals treated with 3 or 6 mg of N in silicone implants were also homogeneous (P = 0.942). The mean diameter of the ovulatory follicle on day 21 was larger in the animals treated with 3 mg of N compared to animals treated with 6 mg of N in two silicone implants ( 13.1 +/- 0.8 vs. 9.7 +/- 0.7 mm, P = 0.005). We conclude that treatment with 3 mg of N in a silicone implant will suppress ovulation in Bos indicus heifers and most cows for 21 d. Six mg of N in two silicone implants will suppress ovulation for 21 d in both cows and heifers.

Silicon Detection in Fat Globules in Pericapsular Tissue of Women and Rats Augmented with Silicone Gel

: Pericapsular adipose tissues of five patients with silicone gel breast implants were examined using electron probe microanalysis (EPMA), a sensitive method for detecting the elemental silicon component of silicone using transmission electron microscopy. All five patients had their implants removed secondary to implant complications. Five experimental animals that received subcutaneous silicone injections were also examined. Intracellular silicon was detected in the adipose tissue and in fat globules of macrophages in all patients and experimental animals. Three forms of intracellular silicon were identified: laminated, granular, and amorphous. No silicon was detected by EPMA in the adipose tissue of human and experimental animal controls. Potential origins of this silicon include the following: silicone gel (PDMS—Poly-dimethylsiloxane), silicone gel that may have been converted to another form, and background silicon from food or environmental sources. The absence of detectable silicon in the control human and animal tissue implicates silicone gel as the probable source. To the best of our knowledge, this is the first description of intracellular silicon within fat globules of both adipocytes and macrophages in recipients of silicone breast implants.?

Severe granulomatous reaction and facial ulceration occurring after subcutaneous silicone injection

Severe granulomatous reaction and facial ulceration occurring after subcutaneous silicone injection

Experimental tissue expansion induces changes in expression of procollagen I and III messenger RNA.

Experimental tissue expansion was performed in nine dogs following placement of subcutaneous silicone balloons. The balloon expander was then filled with 300 ml saline immediately after implantation. Duration of expansion varied from 3 days to 124 days. Unaffected skin and skin over an empty expander served as control tissue. Dermal procollagen I and procollagen III gene expression in response to tissue expansion was investigated by dot-blot analysis using digoxigenin-labeled RNA probes complementary to either human procollagen-alpha 1(I) mRNA or procollagen-alpha 1(III) mRNA. Cross-hybridization of human probes with canine procollagen mRNA was demonstrated by Northern blot analysis. In response to the trauma of surgery, procollagen I and III mRNA transcriptions were found to be decreased significantly within the first few days after implantation. After 9 days of expansion, increased levels of procollagen I mRNA were found, while after 16 days increased levels of procollagen III mRNA were evident. The present study is the first to demonstrate changes in dermal collagen gene expression as a reaction to tissue expansion.

Effect of induced suprabasal progesterone levels around estrus on plasma concentrations of progesterone, estradiol-17β and LH in heifers

A controlled study was carried out to investigate the effects of suprabasal plasma progesterone concentrations on blood plasma patterns of progesterone, LH and estradiol-17β around estrus. Heifers were assigned to receive subcutaneous silicone implants containing 2.5 g (n=4), 5 g (n=4), 6 g (n=3), 7.5 g (n=3) or 10 g (n=4) of progesterone, or implants without hormone (controls, n=5). The implants were inserted on Day 8 of the cycle (Day 0=ovulation) and left in place for 17 d. The time of ovulation was determined by ultrasound scanning. Blood was collected daily from Days 0 to 14 and at 2 to 4-h intervals from Days 15 to 27. Control heifers had the lowest progesterone concentrations on Days 20.5 to 21 (0.5 ± 0.1 nmol L−1); a similar pattern was observed in heifers treated with 2.5 and 5 g of progesterone. In the same period, mean progesterone concentrations in the heifers treated with 6, 7.5 and 10 g were larger (P < 0.05) than in the controls, remaining between 1 and 2.4 nmol L−1 until implant removal. A preovulatory estradiol increase started on Days 16.4 to 18.4 in all the animals. In the controls and in heifers treated with 2.5 and 5 g of progesterone, estradiol peaked and was followed by the onset of an LH surge. In the remaining treatments, estradiol release was prolonged and increased (P < 0.05), while the LH peak was delayed (P < 0.05) until the end of the increase in estradiol concentration. The estrous cycle was consequently extended (P < 0.05). In all heifers, onset of the LH surge occurred when progesterone reached 0.4 to 1.2 nmol L−1. The induction of suprabasal levels of progesterone after spontaneous luteolysis caused endocrine asynchronies similar to those observed in cases of repeat breeding. It is suggested that suprabasal concentrations of progesterone around estrus may be a cause of disturbances oestrus/ovulation.

Effect of Capsulectomy on the Hemodynamics and Viability of Random-Pattern Skin Flaps Raised on Expanded Skin in the Pig

Skin flaps constructed on expanded skin usually include the underlying capsular tissue. It has been hypothesized that capsulectomy may jeopardize the viability of the expanded skin flap. The experiments reported herein were designed to test this hypothesis. Specifically, we studied the hemodynamics and viability of random-pattern skin flaps (8 X 20 cm) raised on delayed bipedicle flaps (group A) and on expanded skin pockets with capsulectomy at the time of flap elevation (group B) or with intact underlying capsular tissue (group C). Each group was randomly assigned to each flank in 16 pigs. Skin pockets were expanded by inflation of subcutaneous silicone tissue expanders with sterile saline (299 +/- 7 ml; X +/- SEM) over a period of 3 weeks. At the end of this period, the bipedicle flaps were constructed. Eight days later, random-pattern skin flaps were raised on bipedicle flaps and skin pockets. The length and area of skin flap viability, judged by the fluorescein dye test performed 1 day postoperatively, were not significantly different (p greater than 0.05) among groups A, B, and C (n = 31 to 32). There also were no significant differences (p greater than 0.05) in total skin capillary blood flow measured 1 day postoperatively (A = 2.6 +/- 0.4, B = 2.4 +/- 0.4, and C = 2.7 +/- 0.6 ml/min per flap; n = 15 to 16) and in skin viability assessed 7 days postoperatively (A = 74 +/- 2, B = 75 +/- 2, and C = 76 +/- 2 percent; n = 16) among delayed skin flaps and skin flaps raised on expanded skin pockets with or without capsulectomy. The results of this flap viability study were confirmed in 5 minipigs in a separate experiment. We conclude that capsulectomy did not have a detrimental effect on the hemodynamics and viability of random-pattern skin flaps raised on expanded skin. Furthermore, we hypothesize that skin flaps raised on expanded skin are similar to delayed skin flaps in that the skin blood flow is optimally augmented; therefore, the capsular tissue does not add significant blood supply to the overlying skin.

Effects of photoperiod, pinealectomy and castration on body weight and daily torpor in Djungarian hamsters (Phodopus sungorus).

During the autumn and winter Djungarian hamsters (Phodopus sungorus) exhibit regression of the gonads, development of a white winter pelage, loss of body weight and daily torpor. These seasonal events are largely regulated by changes in photoperiod. The present experiments were designed to examine the role of the testes and the pineal gland in photoperiodically induced daily torpor and body weight loss. Hamsters displayed a loss of body weight and daily torpor when exposed to a short-day photoperiod in a cold environment, but these phenomena did not occur in hamsters exposed to long days and cold. Testicular regression is probably a precondition for the display of torpor, since daily torpor was almost totally inhibited in hamsters which were exposed to short days and in which testosterone was administered from subcutaneous silicone elastomer implants. Nevertheless, decreased testosterone secretion alone is not a sufficient condition for induction of daily torpor, since torpor was rarely observed in hamsters exposed to long days, even after castration. In addition to decreased testicular activity, the pineal gland is also involved in establishing conditions for torpor. Thus, pinealectomy prevented the display of torpor by castrated hamsters exposed to short days. Body weight changes were also found to be influenced by both testicular hormone and pineal activity. These observations indicate that the pineal gland is involved, as a part of the photoperiodic mechanism, in regulating a variety of physiological events and that some of these actions of the pineal are independent of its extensively described actions on the reproductive axis.

Studies on the control of gonadotrophin release in the gonadectomized male rat: evidence for a lack of involvement of the hypothalamic noradrenergic system in the long-term castrated rat.

The effects of castration with or without testosterone replacement in the adult male rat were studied to investigate possible hypothalamic mechanisms by which changes in gonadotrophin secretion occur at different times after castration, with particular reference to the continuing LH rise and its lack of suppression by testosterone in the long-term castrated rat. Castrated rats received either subcutaneous silicone elastomer implants containing testosterone or empty implants at the time of castration, and a sham-operated group served as controls. At 1, 10 and 40 days after castration, there were six-, 15- and 25-fold rises respectively in LH and 1.5-, two- and fivefold rises in FSH. However, there were no significant changes in hypothalamic noradrenaline concentration and turnover or in alpha-adrenoceptor density and affinity at any time after castration. Testosterone implants were effective in suppressing gonadotrophin release at 1 and 10 days, but not at 40 days after castration, and did not significantly affect hypothalamic noradrenaline turnover or alpha-adrenoceptors at any time. Neither acute inhibition of the noradrenergic system, using either the alpha-adrenoceptor blockers phenoxybenzamine and phentolamine or the synthesis inhibitor alpha-methyl-p-tyrosine, nor chronic depletion of hypothalamic noradrenaline by 6-hydroxydopamine had any significant effect on the normal rise in LH levels seen on days 10 and 40 after castration, and did not alter the ability of testosterone to suppress LH levels. This indicates that, in the long-term castrated rat, the noradrenergic system may not be involved in the control of gonadotrophin release. However, at 16 h after castration, alpha-adrenoceptor blockers and alpha-methyl-p-tyrosine did reduce LH levels, indicating that the noradrenergic system is likely to be involved in the short-term response to castration.

Self-injurious behavior produced in rats by daily caffeine and continuous amphetamine

Self-biting (SB) is an unusual behavioral effect of high doses of certain amphetamine-like drugs in rats. This bizarre behavior has received little attention, perhaps because the high doses of drug required and the dramatic disturbance of the animals' behavioral repertoire have raised the possibility that SB is a high dose phenomenon. However, we have found that continuous administration of very low amounts of amphetamine reliably produces SB in rats, and that this behavioral change can be very selective. We compared SB produced by continuous amphetamine to SB produced by daily caffeine; the latter has been proposed as an animal model for self-injurious behavior (SIB) in the Lesch-Nyhan syndrome. Subcutaneous silicone pellets containing amphetamine base were implanted for 4.5 days; caffeine was administered daily for 10 days. The amphetamine pellets produced the highest rate of SB (75% vs 40%) with the least toxic effects (no deaths vs three deaths). Neither drug produced stereotypy. The dopamine antagonist haloperidol was only marginally effective in controlling SB produced by daily caffeine but the dopamine antagonist pimozide (which has a longer duration of action) prevented SB by amphetamine pellet rats. Continuous release amphetamine pellets may provide an alternative to the caffeine model of SIB in humans, particularly for the Lesch-Nyhan syndrome.

Factors influencing the distribution of antibacterial agents in interstitial tissue fluid: Molecular size and protein binding

The distribution of two aminoglycosides and three penicillins was studied in dogs. Serial samples of interstitial tissue fluid were obtained from subcutaneous silicone rubber capsules and compared with simultaneous serum samples. The results showed the reproducibility of the method both between animals and between experiments. Tobramycin showed a trend to higher serum and tissue fluid concentrations compared to gentamicin but these differences were not statistically significant. The striking differences between the tissue fluid concentrations of ampicillin and cloxacillin were related to the high protein binding of the latter. It is concluded that an adequate tissue fluid concentration requires an adequately maintained serum concentration; drugs that are rapidly excreted and especially those that are highly protein bound, should be given in doses sufficient to produce such a serum concentration.

Changes in morphine self-administration and morphine dependence after lesions of the caudate nucleus in rats.

Rats were trained to bar press for intravenous infusions of morphine sulfate during 1-hr daily test sessions. Small, centrally placed bilateral lesions of the caudate nucleus reduced rats of morphine self-administration to approximately one seventh of preoperative levels; postoperative rates were similar to preoperative rates when the postoperative unit infusion dose of morphine was one tenth of the preoperative dose. Caudate lesions also lowered the threshold dose at which morphine's rewarding property could be detected. Physical dependence was studied in other rats receiving a 3-day continuous infusion of morphine sulfate via implanted subcutaneous silicone reservoirs. Caudate lesions ameliorated withdrawal-induced weight loss and naloxone-induced "wet dog shakes". Both the self-administration and dependence data are consistent with the idea that morphine blocks dopaminergic transmission in the striatum.

Morphine dependence in rats with medial forebrain bundle lesions.

Rats with posterior medial forebrain bundle (PMFB) lesions and control rats were administered morphine chronically for 4 or 5 days via implanted subcutaneous silicone reservoirs. Following cessation of morphine administration after five days, PMFB rats showed less withdrawal-induced weight loss than control rats. Other PMFB and control rats were subjected to forced drinking of morphine solution for 9 days. PMFB rats consumed the morphine solution much more readliy than control rats, whereas intake of a quinine solution was similar in two other PMFB and control groups. These results suggest that the addictive and dependence properties of morphine may have separate mechanisms and based on previously reported neurochemical effects of PMFB lesions, that biogenic amines may be differentially involved in such mechanisms.

A clinical evaluation of subdermal and subcutaneous silicone implants.

A clinical evaluation of subdermal and subcutaneous silicone implants.