Study of intraocular diffusion of ofloxacin in humans and rabbits]

The diffusion of ofloxacin in infected and healthy human and rabbit eyes was investigated. In the human study, cataract surgery patients were given intravenous ofloxacin either as a single 200 or 400 mg dose or as two 400 mg infusions 12 hours apart. Samples of aqueous humor and plasma were collected between 1 and 12 hours after the end of the infusion. Levels in the anterior chamber increased with the dose; peak levels, which occurred after three hours, were 0.33 mg/l after 200 mg and 1.24 mg/l after two 200 mg doses given 12 hours apart. In the rabbit study, 16 hours after experimental infection of the left eye by injection of S. epidermidis into the vitreous, animals were given an intraperitoneal injection of 20 or 50 mg/kg ofloxacin. Dosages in the various ocular tissues showed that penetration into the eye varied with race (albinos greater than pigmented) and dose. Intraocular ofloxacin levels, including in the vitreous, increased two fold when the eye was infected; however, penetration into the sclera, choroid, and retina was comparable in infected and noninfected eyes. These findings in humans and animals suggest that ofloxacin in a dose of a least 400 mg is a useful agent for the treatment of prophylaxis of ocular infections.     

无环鸟苷抗角膜病毒新途径的实验研究

目的 研究用离心法制得的角膜胶原膜载释无环鸟苷的意义。方法 胶原膜载释药物与结膜下注射法按时间把２８只白兔分四组，每组７只，左、右眼对照，对分组采集的房水用高效液相色谱分析法测定其中的药物浓度，做比较分析。结果 ０．５ｈ结膜下注射组房水中无环鸟苷显著高于胶原膜载药组（ｔ＝４．０５，Ｐ〈０．０１）；１ｈ差异无统计学意义（ｔ＝２．０７４，Ｐ〈０．０５），３和５ｈ胶原膜组房水中药物浓度均高于结膜下注射组（ｔ值分别是４．７６１和４．１９０；Ｐ〈０．０１），并可维持较长时间。结论 通过离心法制得的胶原膜给药是胶原膜复合物替代结膜下注射的较好的给药途径。     

An assessment of the ocular safety of excipient maleic acid following intravitreal injection in rabbits

Maleic acid was formulated in 0.7% saline and injected intravitreally in rabbits in order to evaluate ocular safety and tolerability. Maleic acid was formulated within a narrow pH range (2-3), administered in a fixed volume (100 μl), and concentrations ranged from 0.00 to 2.00 mg/eye (0.00 to 12.30 mM vitreous). Ocular evaluations were conducted at 2, 4, and 8 days post injection. Ocular irritation responses were observed at doses from 0.50 mg/eye (3.07 mM vitreous) to 2.00 mg/eye (12.30 mM vitreous) and included conjunctival redness and scleral swelling. Chemosis was observed at 2.00 mg/eye (12.30 mM vitreous). Funduscopic evaluations revealed enlarged retinal blood vessels and optic disk swelling at doses ≥1.50 mg/eye (9.22 mM vitreous), retinal folds and retinal discoloration at 2.00 mg/eye (12.30 mM vitreous). Histopathologic evaluations on days 4 and 8 post injection revealed retinal degeneration at doses ≥1.0 mg/eye (6.15 mM vitreous), conjunctival inflammation at doses ≥1.5 mg/eye (9.22 mM vitreous), and retinal pigment epithelial hypertrophy, optic nerve demyelination, anterior chamber fluid, and conjunctival fibrosis at 2.00 mg/eye (12.30 mM vitreous) maleic acid. The data suggest that maleic acid formulations at ≥1.00 mg/eye (6.15 mM vitreous) were not suitable for intraocular indications.     

Emulsion of amphotericin B in Intralipid 20%: in vitro and in vivo efficacy]

Toxic effects limit the use of amphotericin B (AmB) for the treatment of systemic Candida infections. In vitro and in vivo toxicity can be substantially reduced by mixing AmB with a lipid emulsion used for parenteral nutrition, intralipid 20% (IL). This study was designed to evaluate the potential effects of IL on the activity of Amphotericin B against Candida. A clinical strain of Candida albicans was used. AmB deoxycholate (Fungizone) was reconstituted in a 5% glucoce solution (AmB-G5), in 3 mg/ml IL (AmB-IL3) or in 1.5 mg/ml IL (AmB-IL 1.5). Minimum inhibitory concentrations and minimum lethal concentrations were 0.4 mg/l and 2.5 mg/l, respectively, with AmB-G5, 0.1 mg/l and 1 mg/l with AmB-IL3, and 0.24 mg/l and 1 mg/l with AmB-IL 1.5. In vitro killing curves with 0.1 mg/l, 0.25 mg/l, and 2.5 mg/l AmB were determined with the following results: 1) with 0.1 and 0.25 mg/l AmB, fungicidal activity was seen with AmB-IL3 and AmB-IL 1.5 but not with AmB-G5; 2) with 2.5 mg/l AmB, fungicidal activity was less marked with AmB-G5 (-1.7 log CFU/ml after 24 hours) than with AmB-IL3 and AmB-IL1.5 (-4.3 log CFU/ml and -4.2 log CFU/ml, respectively, after 24 hours; p less than 0.05). In rabbits given a single intravenous injection of 4 mg/kg AmB, analysis of infected subcutaneous fibrin clots detected measurable concentrations of AmB beyond the 24th-36th hour, with levels of 0.5 mg/l for AmB-G5 and 1 mg/l for the two AmB-IL preparations over a period of three days.(ABSTRACT TRUNCATED AT 250 WORDS)     

微透析和高效液相色谱检测万古霉素在清醒兔眼玻璃体内的浓度

背景：万古霉素玻璃体内注射后的药代动力学资料较少。 目的：观察万古霉素玻璃体腔内注射后在清醒兔眼玻璃体内的浓度。 方法：将微透析探针植入清醒正常兔眼和细菌性眼内炎兔眼玻璃体内24 h后,向玻璃体内注射10 g/L万古霉素0.1 mL,利用微透析采样技术联合高效液相色谱法连续检测万古霉素注射后0.5,1,2,4,6,12,24,48,72,84 h,兔眼玻璃体内的药物浓度。 结果与结论：万古霉素在正常兔眼玻璃体内的代谢呈开放式二室模型,玻璃体内的峰值浓度为695.92 mg/L,半衰期51.66 h;在细菌性眼内炎兔眼玻璃体内的代谢呈一室模型,万古霉素的峰值浓度为713.35 mg/L,半衰期为11.91 h。所有动物给药84 h,玻璃体内万古霉素的浓度均高于最小抑菌浓度。实验在动物清醒状态下实时、连续、动态采样,检测结果准确,能满足万古霉素药动学分析的需要。     

Piperacillin-amikacin combinations: killing curves

Bactericidal activity as a function of time of piperacillin (PIP) and amikacin (AKN) alone and in combination was evaluated by killing curves technique on 23 clinical isolates: E. coli (6), K. pneumoniae (5), E. cloacae (6) and P. aeruginosa (6), for which the minimal inhibitory concentrations ranges of piperacillin were 0.25 to 64 mg/l and of amikacin 1 to 8 mg/l. For each species, the strains were chosen according to the most frequent phenotypes: beta-lactams susceptible, penicillinase (Pase), cephalosporinase (Case) and Pase + Case producers. Killing curves were carried out with the following concentrations (mg/l): piperacillin (2, 16, 64); amikacin (4, 8, 16); piperacillin (2) + amikacin (4); piperacillin (16) + amikacin (8); piperacillin (64) + amikacin (16). Antibiotic concentrations corresponded to pharmacokinetics and/or to critical values of piperacillin and amikacin. Bactericidal activity was defined as a 4 log 10 decrease in CFU/ml between 2 and 24 hours. When piperacillin (64) was combined with amikacin (16), the bactericidal effects were nearly the same as those with amikacin alone. But piperacillin (16) + amikacin (8) combination had bactericidal effect for the majority of strains (21/23) and it prevented for some of them the bacterial regrowth observed with amikacin alone at the same concentration. A bactericidal activity without regrowth (until the 24th hour) was obtained for 9 strains; 2 susceptible E. coli, 3 K. pneumoniae (chromosomal Pase producer) and 4 cefotaxime susceptible E. cloacae, with low dose combination piperacillin (2) + amikacin (4). Finally, only combinations piperacillin (64) + amikacin (16) or piperacillin (16) + amikacin (8) had bactericidal activity on 2 Ticarcillin-resistant P. aeruginosa, the two antibiotics being separatedly bacteriostatic.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune privilege persists in eyes with extreme inflammation induced by intravitreal LPS.

Since immune privilege is believed to exist in the eye in order to suppress sight-destroying inflammation, we wondered whether eyes with intraocular inflammation retain the immune privileged state. Intraocular inflammation was induced by injection of lipopolysaccharide (LPS) into the vitreous cavity of BALB/c mouse eyes, which showed a peak in intensity at approximately 9 h. At this time point, inflamed eyes were examined for their capacity to afford immune privilege to injected allogeneic tumor cells, and to promote anterior chamber-associated immune deviation (ACAID) to antigens injected locally. In addition, aqueous humor (AqH) harvested from inflamed eyes was tested for its ability to suppress T cell activation. Surprisingly, eyes with acute, intense intraocular inflammation allowed allogeneic tumor cells to form progressively growing tumors, and these same eyes promoted ACAID. Moreover, AqH harvested from inflamed eyes strongly inhibited T cell activation. We conclude that the type of extreme, intraocular inflammation evoked by intravitreally injected LPS fails to abolish immune privilege in the eye. These findings are discussed in light of the effects of other types of inflammation on the integrity of ocular immune privilege, and with respect to the capacity of the eye to maintain immune privilege by more than one mechanism.     

A thymidine kinase deficient HSV-2 strain causes acute keratitis and establishes trigeminal ganglionic latency,but poorly reactivates in vivo

The incidence of herpetic keratitis following in-tranasal or direct ocular infection with thymidine kinase-negative (TK^?) strains of herpes simplex virus (HSV)-2 has not been well studied, and the role of the TK gene in the establishment of latency and virus reactivation is controversial. To determine whether a TK^? strain of HSV-2 could establish trigeminal ganglionic latency and be reactivated in vivo to produce recurrent keratitis or nervous system infection, an animal model of acute and recurrent infection was utilized. Rabbits were infected by the intranasal or ocular routes, and latency was reactivated by immuno-suppression. Virus shedding in nasal and ocular secretions was monitored, and the eyes were examined for the presence of corneal epithelial lesions during acute and reactivated infections. Central nervous system (CNS) and trigeminal ganglionic tissues were assayed by histologic, virologic, and in situ hybridization techniques. All rabbits intranasally infected shed virus in both ocular and nasal secretions, whereas only 30% of rabbits infected in the eyes shed virus in nasal secretions. Virus was recovered from co-cultivation cultures, but not from cell-free ho-mogenates, of trigeminal ganglionic and CNS tissues from animals inoculated by both routes. The incidence of keratitis was much greater after direct ocular inoculation, although both routes of inoculation produced CNS and ganglionic inflammatory lesions. Keratitis healed in 92% of the animals infected by the ocular route by 26 days post infection. Of rabbits initially infected in the eyes and then subjected to drug-induced reactivation, only 30% shed virus, which was limited to a 24 hour period; there was no reappearance of epithelial keratitis, no animal became blind, and none died. In contrast, latently infected control rabbits uniformly reactivated. These studies show that this TK^? HSV-2 strain (i) replicates in the eye, (ii) is neuroinvasive but non-neurovirulent following intranasal and direct ocular infection; (iii) sheds in the eye more frequently and for longer periods after ocular than after intranasal inoculation; (iv) induces epithelial keratitis that usually heals spontaneously; (v) establishes latency in trigeminal ganglionic neurons, but no other ganglionic cells; and, (vi) reactivates in a small proportion of animals, but does not produce recurrent ocular lesions following drug-induced immunosuppres-sion. Thus, the TK gene appears directly involved in HSV latency and reactivation in vivo. © 1994 Wiley-Liss, Inc.     

Intra aqueous humor penetration of ciprofloxacin in humans

Authors have studied the penetration of ciprofloxacin in the aqueous humor of 30 patients (30 eyes). The concentration in the anterior chamber was on average 0.73 mg/l (33% of serum level), from 1.30 hours after a single oral dose (1000 mg) till the 5th hour after this dose. The samples were assessed by a microbiological method. These results are over the minimal inhibitory concentration for many bacterial agents found in endophthalmitis. So this antibiotic may be proposed in the treatment of endophthalmitis, with further investigations assessing the safety of this procedure.     

The effect of corticosteroids or nitrogen mustard on aqueous humor chemotactic activity induced by intravitreal endotoxin

In rabbits intravitreal injection of endotoxin induces potent chemotactic activity for monocytes in aqueous humor. We have assessed the effect of methylprednisolone (30 mg/kg intramuscularly) or nitrogen mustard (1.75 mg/kg intravenously) on the generation of this chemotactic activity. Histologic changes, anterior chamber protein extravasation, and aqueous humor cellular infiltration were reduced by corticosteroids to a variable degree. However, even in animals with a marked reduction in protein extravasation or histologic change, chemotactic activity was substantially preserved. Similarly, nitrogen mustard induced a leukopenia without affecting the ability of endotoxin to generate chemotactic activity in aqueous humor. In contrast, corticosteroids reduced both protein extravasation and the generation of chemotactic activity induced by intravenously injected endotoxin. The results suggest that the chemotactic activity induced in the eye by intravitreal endotoxin may be locally synthesized and may be present without a substantial leukocytic infiltrate.     

Aqueous prostaglandin E2 and intraocular pressure after argon laser trabeculoplasty in glaucoma patients pretreated with topical piroxicam

Intracameral injection of prostaglandin E2 causes an increase in intraocular pressure (IOP) in rabbits, cats, and monkeys. Arachidonic acid administered topically in rabbits and monkeys also increases IOP. The effect of prostaglandin E2 on IOP in human eyes is unclear. We performed paracentesis of the anterior chamber one hour after 180 degrees argon laser trabeculoplasty in cases of primary open-angle glaucoma. This laser treatment may increase IOP, but no correlation was found between post-operative IOP changes and PGE2 levels. PGE2 was significantly lower in ten eyes pretreated with topical piroxicam, a prostaglandin biosynthesis inhibitor (7 +/- 6 pg/ml), than in ten untreated eyes (443 +/- 232 pg/ml) and five controls. No significant difference was found between post-operative IOP in eyes pretreated and untreated with piroxicam. The low levels of PGE2 in the aqueous humour of eyes pretreated with piroxicam indirectly demonstrated the transcorneal penetration of the topically-administered drug, and the effectiveness of piroxicam in inhibiting the ocular synthesis of PGE2.     

Macrophage-induced glomerular injury. Cell transfer studies in passive autologous antiglomerular basement membrane antibody-initiated experimental glomerulonephritis

The current studies were designed to assess the ability of mononuclear inflammatory cells to mediate glomerulonephritis (GN) by studying the effects of replacement of mononuclear inflammatory cells in rabbits depleted of all circulating leukocytes and in which an antibody-initiated, macrophage-dependent model of glomerular injury was induced. GN was initiated by the injection of passive autologous rabbit antisheep gamma-globulin serum following the injection of sheep antirabbit glomerular basement membrane antibody. A proliferative endocapillary GN regularly occurred in which macrophages were the predominant infiltrating cell (mean 48.4 +/- 16.1 SD macrophages/glomerulus) and heavy proteinuria developed (590 +/- 152 mg/24 hours). This lesion was shown to be dependent on the presence of circulating leukocytes as prior treatment with nitrogen mustard producing panleukopenia completely prevented macrophage accumulation (0.4 +/- 0.1 macrophages/glomerulus), abnormal proteinuria (5.1 +/- 1.6 mg/24 hours), and histologic evidence of injury. When peritoneal mononuclear inflammatory cells were given intravenously (10(8] to nitrogen mustard-treated rabbits that were given the GN-inducing antibodies, a proliferative GN developed with significant macrophage accumulation (14.2 +/- 4.8 macrophages/glomerulus), and some rabbits became proteinuric (38.8 +/- 15.3 mg/24 hours). Electron microscopy indicated that glomerular endothelial cells underwent swelling and separation from the basement membrane in relation to macrophage accumulation. Control nitrogen mustard-treated animals given 10(8) mononuclear inflammatory cells without the injection of disease-initiating antibodies did not have glomerular macrophage accumulation (0.8 +/- 0.3 macrophages/glomerulus), abnormal proteinuria (6.1 +/- 2.1 mg/24 hours), or any histologic abnormality. Thus, macrophages can accumulate in glomeruli in direct response to the deposition of antibody and produce a proliferative GN by both their own accumulation and their effects on intrinsic glomerular endothelial cells.     

Diffusion of fosfomycin into the human and rabbit eye (aqueous humor and vitreous body)

The intraocular distribution of fosfomycin was studied in 32 patients undergoing cataract surgery and in 8 rabbits after experimental infection of one eye by Staphylococcus aureus. Concentrations found 1 to 6 hours after termination of a 4 g fosfomycin infusion ranged from 14 to 18.8 mg/l in the aqueous humor and 8 to 12.5 mg/l in the vitreous body. These levels are higher than the MICs for 80 to 90% of the bacteria responsible for endophthalmitis. In each rabbit, the fosfomycin concentration in the infected eye as compared to the healthy eye was increased 2.5 to 5--fold for the aqueous humor and 4.9 to 19.2--fold for the vitreous body. Fosfomycin, in association with a third generation cephalosporin (ceftriaxone) or one of the new quinolones (pefloxacin) can be recommended for the prevention or early treatment of endophthalmitis.     

Actions and interactions of bradykinin,prostaglandins, and nonsteroidal antiinflammatory agents on the eye

Intracameral injections of bradykinin into the eyes of rabbits anesthetized with urethane were found to produce a dose-dependent constriction of the pupil and increase in the amount of protein present in the aqueous humor. Both these effects were relatively fast in onset, pupillary constriction being observed 1–2 min after the injection. The intact bradykinin molecule was required to produce these effects since prior incubation of known amounts of bradykinin with chymotrypsin and subsequent intracameral injection were without effect. No kininase activity was observed in samples of normal aqueous humor, however, kininase activity was present in aqueous humor removed from eyes inflamed by either paracentesis or nitrogen mustard. The actions of bradykinin on both the pupil and the protein content of aqueous humor were markedly reduced or abolished by pretreatment with inhibitors of prostaglandin biosynthesis, such as indomethacin or pirprofen, given either topically or by intraperitoneal injection. In these animals the simultaneous injection of prostaglandin Ez together with the bradykinin restored the ocular responses to normal. These results suggest that prostaglandins contribute to the ocular actions of bradykinin.This work was supported in part by USPHS grants EY 00457 and EY 00091 and USPHS Training Grant GM 00438.     

IL-10 in vivo gene expression in a cell-induced animal model of proliferative vitreoretinopathy

Due to inhibitory activities on cell-mediated immune responses, interleukin-10 (IL-10) has been proposed as a good candidate to treat inflammatory eye disease and proliferative vitreoretinopathy (PVR). In this study we evaluate the effect of human IL-10 (hIL-10) expression in a cell-induced animal model of PVR. Rabbit dermal fibroblasts were genetically modified by infection with retroviral particles carrying the neomycin resistance gene (neoR) alone or in combination with the hIL-10 gene. PVR was induced in rabbits by intravitreal injections of RDF hIL-10 or RDF neo. Some rabbits received instead injections of soluble recombinant hIL-10 (rhIL-10). PVR was graded by fundoscopy. Eyes were enucleated for histology at day 28. ELISA was performed to measure hIL-10 production in RDF supernatants and in vitreous samples, 24 h after injection. Results showed that in vitro hIL-10 production by RDF was 24,500 pg/10(6) cells/ml/24 h. In vivo IL-10 secretion was detected in all rabbits injected with RDF hIL-10 but was undetectable in control rabbits. Similar clinical grades of PVR were found in rabbits injected with RDF hIL-10 or RDF neo. Histology showed that all eyes injected with RDF hIL-10 had significant inflammatory infiltration whereas only one control eye was clearly inflamed. Rabbits injected with soluble rhIL-10 had normal fundoscopy and normal histology. In conclusion, our results show that in vivo, in a cell-induced model of PVR, hIL-10 has no effect in the clinical progression of PVR. Histology, however, shows that pro-inflammatory effects seem to overcome its suppressive properties.     

Effect of intravenous tuftsin administration on histamine concentration in tissues of rabbits and guinea-pigs.

The performed studies covered the effect of tuftsin, tetrapeptide stimulating many components of immunological reactions, to histamine concentration in lungs, kidneys, liver, duodenum as well as in the blood of rabbits and guinea-pigs. Tuftsin was given intravenously in a single injection (0.5 mg/kg), and for guinea-pigs also in one-hour infusion (1.0 mg/kg/h). The tissue designed for determining the histamine concentration by spectrofluorimetric method were taken 1 hour after introduction of the peptide. It has been found out that tuftsin changes the histamine concentration in tissues, lowering it in the lungs, and elevating it in the kidneys and liver. The changes in duodenum and blood were insignificant.     

马来酸桂哌齐特对大鼠颅脑损伤作用效果的实验研究

目的脑损伤后脑血管自发调节功能受损导致脑组织缺血缺氧是继发性脑损伤发病机理的重要环节。及时改善创伤后脑组织缺血缺氧状态对于创伤性脑损伤的预后极为重要。本研究对新型脑血管治疗药物克林澳(马来酸桂哌齐特注射液)在创伤性脑损伤中的神经保护作用进行探讨。方法雄性Sprague-Daw-ley大鼠50只,随机分三组:假手术组(n=20),中度液压脑损伤组(1.8~2.2atm)(n=20)(生理盐水3.0mg/kg静脉注射,30min and 24h post-injury),药物组:(克林澳3.0mg/kg静脉注射,30min and 24h post-injury)(n=10),于损伤后72h分别检测创伤侧及对侧皮层、海马及丘脑病理损伤。应用水迷宫实验对大鼠神经功能进行评价。结果脑损伤后皮层,海马以及丘脑神经元大量损伤,早期应用克林澳显著减轻创伤后神经元损伤。皮层、海马及丘脑分别减轻51%、35%、26%(P<0.05)。水迷宫实验平均上台时间及上台前游动总距离较对照组显著减少(P<0.05)。结论脑损伤后早期应用克林澳能显著减轻神经组织的病理损害,并改善神经功能。     

大肠杆菌内毒素诱导的SD大鼠眼内炎

目的 观察细菌内毒素脂多糖(LPS)诱导的大鼠眼内炎性反应的临床、组织病理学和血眼屏障的特点.方法 SD大鼠玻璃体腔内注人大肠杆菌LPS(1μg)建立LPS诱导的眼内炎动物模型,对照组注入无菌生理盐水.在LPS注入后6h至7d的不同时点,分别对眼部炎性反应评分、浸润白细胞计数、前房水蛋白质浓度和玻璃体内LPS水平进行测定和评估.结果 在LPS注射后6～72 h眼内可见严重的炎性反应,至术后7d炎性反应基本消退.眼内白细胞的浸润数量在术后24h达到高峰[(1182.63±191.15)细胞/眼],至术后3 d浸润细胞数量迅速下降[(331.25±57.9)细胞/眼].在各观察时点,均可观察到眼内炎组房水蛋白质浓度较对照组显著增高(P<0.01). LPS注入眼内后前3 d,玻璃体腔内LPS含量迅速下降[前3d分别为(327.02±51.54)、(176.0±53.68)和(54.91±13.26)ng],在7d后玻璃体腔内LPS基本被清除.结论 大肠杆菌内毒素在SD大鼠可诱导出严重的实验性眼内炎,大量白细胞眼内浸润、血眼屏障破坏和玻璃体腔自发性细菌成分清除是本实验性眼内炎模型的主要病理特点.     

The effect of acetazolamide on the kinetics of four newer β-lactams in the aqueous humor

Objective   To evaluate whether the effect of acetazolamide on piperacillin's aqueous humor concentrations observed in animals exists also in humans for ceftazidime, cefotaxime, ceftriaxone and aztreonam.
Methods   One hundred and eighty-eight patients undergoing eye cataract surgery were randomly allocated to receive intravenous ceftazidime, cefotaxime, aztreonam or ceftriaxone with (subgroup A) or without (subgroup B) concomitant oral administration of acetazolamide. Antibiotic concentrations in serum and the aqueous humor, simultaneously sampled during the operation, were measured using an agar well diffusion technique, and the ratios of the concentrations of aqueous humor to serum were calculated and compared. Statistical analysis was performed by using the paired t -test.
Results   Mean aqueous humor ceftazidime concentrations at 2, 4 and 6 h were 24.65, 16.4 and 8.6 mg/L (subgroup A), and 4.26, 8.66 and 5.61 mg/L (subgroup B). Corresponding concentrations of cefotaxime were 1.75, 1.0 and 0.77 mg/L (subgroup A), and 1.11, 0.81 and 0.58 mg/L (subgroup B), and of aztreonam 6.9, 5.84 and 3.61 mg/L (subgroup A), and 3.38, 2.57 and 1.48 mg/L (subgroup B). Ceftriaxone concentrations at 2, 4, 6 and 12 h were 1.78, 1.49, 1.57 and 1.41 mg/L (subgroup A), and 1.35, 0.95, 1.08 and 0.85 mg/L (subgroup B). The differences in aqueous humor concentrations when acetazolamide was administered were statistically significant ( P  < 0.05), with the exception of ceftazidime 6 h, cefotaxime 6 h and ceftriaxone 2 h.
Conclusions   Although acetazolamide resulted in statistically significant increases in the aqueous humor concentrations of all the antibiotics tested, this effect was most marked for ceftazidime.     

Biocompatibility of elastin-like polymer poly(VPAVG) microparticles: in vitro and in vivo studies

Poly(L-valine-L-proline-L-alanine-L-valine-L-glycine) (VPAVG) is a new kind of proteinaceous polymer belonging to the Elastin-like family. These polymers are based on the recurrence of certain short peptide monomers that are considered as "building blocks" in the natural elastin. This smart thermoresponsive polymer has the ability to self-associate at physiological temperature to form aggregates with about 60% in water. This ability can be harnessed to prepare microparticles loaded with an active substance. The aim of this report is to evaluate, from the results of the experiment conducted, the biocompatibility of microparticles prepared from poly(VPAVG). We have studied the cytotoxic effects of microparticles, edema formation after subcutaneous injection (1 and 2.5 mg) in rats (n = 6), and also intraocular tolerance after the intravitreal injection of 2.5 mg of poly(VPAVG) microparticles into pigmented rabbits (n = 12). The polymer did not induce any cytotoxicity or nonspecific depression of cellular respiration on macrophages under the range of polymer concentrations investigated in this study (20, 30, 40, and 60 mg/mL). We observed no inflammatory response to microparticles after subcutaneous injection in the hind-paw of rats, with no significant differences between the control group (PBS) and experimental groups. Anterior and posterior segment signs were evaluated after intraocular injection of poly(VPAVG) microparticles. Only a few eyes (2/11) of the experimental group presented inflammation signs at day 28 postinjection. Nevertheless, 45% (5/11) of the eyes receiving microparticles showed tractional retinal detachment. The results observed in this work suggested certain fibroblastic activity induced by poly(VPAVG) microparticles after their intraocular injection.