Significance of nasal septal deviation among patients with antrochoanal polyp.

OBJECTIVE: This study aimed to examine the association between nasal septal deviation and antrochoanal polyp. METHODS: This was a retrospective review of medical records and imaging of patients who underwent endoscopic sino-nasal surgery for antrochoanal polyp. RESULTS: Forty-eight patients operated on for antrochoanal polyp between 2009 and 2019 were eligible for the study. The median age was 32 years, and 52.1 per cent were male. Antrochoanal polyp was diagnosed equally in the right and left nasal cavities. Septal deviation was present in 77 per cent of such cases. In 44 per cent of septal deviation cases, the antrochoanal polyp was ipsilateral to the deviation, which was not statistically significant. The type of deviation according to the Mladina classification was not correlated with the laterality of septal deviation and antrochoanal polyp. CONCLUSION: The laterality of the septal deviation was not found to be correlated with that of the antrochoanal polyp. Therefore, performing routine septoplasty during antrochoanal polyp surgery is unnecessary unless the deviation interferes with the complete extraction of the polyp.

α-Lipoic acid blocks the GMCSF induced protease/protease inhibitor spectrum associated with fetal membrane weakening in-vitro.

INTRODUCTION: We use an in-vitro human fetal membrane (FM) explant-based model to study inflammation-induced FM weakening, a prerequisite for PPROM. In this system, GMCSF is a critical intermediate, both necessary and sufficient for TNFα and thrombin induced FM weakening. α-Lipoic-acid (LA) blocks TNFα and thrombin, as well as GMCSF-induced weakening. Recently, we reported LA concomitantly blocks GMCSF-induction of MMPs 2, 9 and 10 and inhibition of TIMPs 1-3. The aim of this study was to show that LA blocks GMCSF-induced increases in additional proteases and reductions in additional protease inhibitors. METHODS: FM fragments were cultured±LA and then±GMCSF. In other experiments, weak versus strong, fresh FM were cultured without additions. Fragments were strength tested and media analyzed by multiplex protein ELISA for proteases and protease inhibitors. RESULTS: GMCSF induced FM weakening and concomitantly increased several Proteases (Cathepsin-S, Proteinase-3, Elastase-2) and decreased several protease inhibitors (NGAL, Cystatin-C, HE4 and Thrombospondin1). LA inhibited GMCSF-induced FM weakening and all enzymatic changes. Untreated weaker versus stronger regions of fresh FM showed comparable differences in proteases and protease inhibitor patterns to GMCSF-stimulated versus controls. CONCLUSION: LA blocks GMCSF-induced human FM weakening and associated protease increases and inhibitor decreases. The GMCSF-induced spectrum of protease/protease-inhibitor changes is similar to that in the natural weak FM fragments. In concert with previously reported GMCSF-induced changes in MMPs & TIMPs, these other protease and protease-inhibitor changes presumably facilitate FM weakening and rupture. LA blocks these GMCSF effects and therefore may be a useful agent to prevent PPROM.

Closed-suction compared with Penrose drainage after free flap reconstruction in the head and neck.

Microsurgical free flaps are common in head and neck reconstruction, and their techniques and outcomes have continuously improved during the past decades. However, there are variations in practice among surgeons between the use of closed-suction drainage systems and Penrose drains. The proponents of Penrose drains propose that the negative pressure generated by the closed-suction drainage system may harm the microvascular anastomosis. We know of no previous studies that have compared the two drains for microvascular free flap reconstruction, so our aim was to compare them in a single-centre, retrospective review of all patients who had microvascular free flap reconstruction of the head and neck region in our department between 1 November 2010 and 1 September 2017. During this period 84 patients had 87 free flap reconstructions in the head and neck, 43 of which had Penrose, and 44 closed-suction, drainage. We compared the number of complications between the groups including haematomas, seromas, wound infections, anastomostic thrombosis, anastomotic revision, and need for re-exploration. There were no significant differences between the groups, despite a trend toward fewer negative explorations in the closed-suction group. There were no differences in complications between suction and passive drainage systems after microvascular free flaps, which suggests that closed suction drainage could be safely used after free flap reconstruction in the head and neck.

Prognostic value of lymph node ratio in metastatic papillary thyroid carcinoma.

OBJECTIVE: Cervical metastases in papillary thyroid carcinoma are associated with increased recurrence. However, their effect on survival remains controversial. This study evaluated literature on the prognostic value of lymph node ratio for loco-regional recurrence and survival in metastatic papillary thyroid carcinoma. METHODS: The PubMed database was systematically searched using the terms 'papillary thyroid carcinoma' and 'lymph node ratio'. Articles addressing the association between lymph node ratio and loco-regional recurrence or survival were identified. RESULTS: Nine retrospective studies were included, comprising 12 400 post-thyroidectomy and neck dissection papillary thyroid carcinoma patients (median age, 48.6 years; 76 per cent females). Lymph node ratio was associated with worse recurrence-free survival in 60 and 75 per cent of studies investigating the effect of central compartment metastases and both central and lateral compartment metastases on recurrence-free survival, respectively. One large population-based study showed an association between lymph node ratio and disease-specific mortality in N1 nodal disease, but failed to maintain the same association when N1b patients were excluded. CONCLUSION: Regional lymph node ratio is an independent predictor for loco-regional recurrence in pathologically staged N1 patients with papillary thyroid carcinoma. Patients with a high lymph node ratio should be closely followed up.

Visceral basidiobolomycosis: An overlooked infection in immunocompetent children.

Visceral basidiobolomycosis is an unusual fungal infection of viscera caused by saprophyte Basidiobolus ranarum. It is very rare in healthy children and poses a diagnostic challenge due to the non-specific clinical presentation and the absence of predisposing factors. We report a case of gastrointestinal basidiobolomycosis in a 4-year-old healthy girl who presented with a short history of abdominal pain, bleeding per rectum, fever, and weight loss. The diagnosis was based on high eosinophilic count, classical histopathology findings of fungal hyphae (the Splendore-Hoeppli phenomenon), and positive fungal culture from a tissue biopsy. Fungal infection was successfully eradicated with a combined approach of surgical resection of the infected tissue and a well-monitored course of antifungal therapy. The atypical clinical presentation, diagnostic techniques, and the role of surgery in the management of a rare and lethal fungal disease in an immunocompetent child are discussed.

Utility and impact of early t(15;17) identification by Fluorescence In Situ Hybridization (FISH) in clinical decision making for patients in Acute Promyelocytic Leukemia (APL).

INTRODUCTION: Acute Promyelocytic Leukemia (APL) is a curable malignancy with studies showing above 90% survival. However, population-based studies looking at survival suggest that approximately 30% of patients with APL die during induction. Early demonstration of t(15;17) will lead to accurate decision making regarding treatment. The aim of this project was to validate earlier time frames for the Abbott Molecular Vysis LSI promyelocytic leukemia (PML)/ retinoic acid receptor alpha (RARA) fluorescence in situ hybridization (FISH) probe (ASR 6-16 h). METHODS: Twenty patients (15 APL cases and five non-APL cases) were selected for validating various hybridization times for the FISH probe. Expected normal signal pattern was two red and two green signals (2R2G), and the most common expected abnormal signal pattern was two fusion (yellow) signals, one red and one green (2F1R1G) and/or one fusion, one red and one green (1F1R1G). RESULTS: The specificity of the probe ranged from 84% at 2 h, 86% at 4 h, 84% at 6 h, and 87% for overnight hybridization. The sensitivity increased from 79% at 2 h, 80% at 4 h, 81% at 6 h to 87% for overnight hybridization. CONCLUSION: Based on the validation studies, we recommend reading of FISH results at the 4-h incubation mark for a preliminary diagnosis and confirmation with overnight hybridization.

Decidual GM-CSF is a critical common intermediate necessary for thrombin and TNF induced in-vitro fetal membrane weakening.

INTRODUCTION: Inflammation/infection and decidual bleeding/abruption are highly associated with pPROM. As no animal model for pPROM exists, we have developed an in-vitro model system for the study of human fetal membrane (FM) weakening/rupture. Using it we have demonstrated that both TNF/IL-1 (modeling inflammation) and thrombin (modeling bleeding) weaken full thickness FM in a dose dependent manner concomitant with inducing biochemical changes similar to those seen in the FM physiological weak zone. METHODS: As the physiological site of infection and bleeding is the choriodecidua (CD), we modified our model system with full thickness FM tissue mounted on modified Transwell culture inserts to permit directional TNF/thrombin exposure on the decidua only (rather than both sides of the FM). After incubation, medium was sampled separately from the CD facing (maternal side) or from the amnion facing (fetal side) compartments and probed for cytokine release and confirmed with western blots. The FM was strength tested within the insert. RESULTS: Full-thickness FM fragments exposed to TNF or thrombin on CD side only showed dose dependent weakening and biochemical changes consistent with previous reports. Concomitantly, GM-CSF increased markedly on the CD but not the amnion side. Numerous proteases including MMP1 and MMP3 also increased on the CD side. Pre-incubation with GM-CSF antibody blocked both thrombin and TNF induced weakening. Finally, GM-CSF weakened FM in a dose dependent manner. DISCUSSION: GM-CSF is a critical common intermediate in the thrombin and TNF FM weakening pathways.

Antibiotic cement-coated rods: an effective treatment for infected long bones and prosthetic joint nonunions.

The treatment of infected nonunions is difficult. Antibiotic cement-coated (ACC) rods provide stability as well as delivering antibiotics. We conducted a review of 110 infected nonunions treated with ACC rods. Patients were divided into two groups: group A (67 patients) with an infected arthrodesis, and group B (43 patients) with an infected nonunion in a long bone. In group A, infected arthrodesis, the success rate after the first procedure was 38/67 (57%), 29/67 (43%) required further surgery for either control of infection or non-union. At last follow-up, five patients required amputation, representing a limb salvage rate of 62/67 (93%) overall. In all, 29/67 (43%) presented with a bone defect with a mean size of 6.78 cm (2 to 25). Of those with a bone defect, 13/29 (45%) required further surgery and had a mean size of defect of 7.2 cm (3.5 to 25). The cultures were negative in 17/67 (26%) and the most common organism cultured was methicillin-resistant staphylococcus aureus (MRSA) (23/67, (35%)). In group B, long bones nonunion, the success rate after the first procedure was 26/43 (60%), 17/43 (40%) required further surgery for either control of infection or nonunion. The limb salvage rate at last follow-up was 43/43 (100%). A total of 22/43 (51%) had bone defect with a mean size of 4.7 cm (1.5 to 11.5). Of those patients with a bone defect, 93% required further surgery with a mean size of defect of 5.4 cm (3 to 8.5). The cultures were negative in 10/43 (24%) and the most common organism cultured was MRSA, 15/43 (35%). ACC rods are an effective form of treatment for an infected nonunion, with an acceptable rate of complications.

The effects of thrombin and cytokines upon the biomechanics and remodeling of isolated amnion membrane, in vitro.

Abruption-induced thrombin generation and inflammation/infection induced cytokine production have both been associated with fetal membrane (FM) weakening and preterm premature rupture of the fetal membranes (PPROM). Using our in vitro model system we have demonstrated that thrombin, and separately the cytokines, tumor necrosis factor-alpha (TNFα) and interleukin-1-beta (IL-1ß), remodel and weaken full thickness FM. Additionally, we have reported that the anti-oxidant and NFκB inhibitor, alpha-lipoic acid (LA), blocks these thrombin and cytokine induced effects. The purpose of these studies was to determine whether thrombin and cytokines directly weaken the amnion membrane (AM), the major load-bearing component of FM. Isolated AM or full thickness FM fragments from unlabored Cesarean deliveries were incubated with thrombin, TNFα, or IL-1ß, for 48 h. Rupture strength (breaking force) of each fragment was thereafter determined using our published methodology. Biochemical evidence of remodeling and apoptosis; immunoreactive Matrix Metalloproteinase 9 (MMP9), Tissue Inhibitor of Matrix Metalloproteinase 3 (TIMP3) and cleaved poly (ADP-ribose) polymerase (C-PARP) levels in tissue extracts, were determined by western blot and densitometry. Thrombin induced a dose-dependent weakening of isolated AM (P < 0.001) coupled with dose dependent increases in PARP cleavage, and reciprocal increases and decreases, respectively, in MMP9 and TIMP3 protein (all P < 0.01). Thrombin receptor activating peptide-6 (TRAP) also weakened isolated AM. Neither TNFα nor IL-1ß weakened isolated AM. However, both cytokines weakened AM when it was incubated together with the choriodecidua as part of full thickness FM (P < 0.001). Cytokine-conditioned choriodecidua medium also weakened isolated AM (P < 0.001). Under conditions in which cytokines weakened the AM, the changes in MMP9, TIMP3 and PARP cleavage were consistent with those seen after thrombin incubation. LA blocked the FM weakening and remodeling effects. In summary, thrombin weakens AM directly whereas cytokines weaken AM indirectly by causing the release of soluble intermediates from the choriodecidua.

Alpha-lipoic acid inhibits thrombin-induced fetal membrane weakening in vitro.

Cytokine-mediated inflammation and abruption-induced thrombin generation are separately implicated in matrix metalloproteinase (MMP)-mediated weakening of fetal membranes (FM) leading to preterm premature rupture of the fetal membranes (PPROM). At term, FM of both labored vaginal and unlabored Cesarean deliveries exhibit a weak zone overlying the cervix exhibiting ECM remodeling characterized by increased MMP9 protein and activity. We have reproduced these biochemical changes as well as FM weakening in vitro using tumor necrosis factor-alpha (TNF) and interleukin (IL)-1ß, inflammatory cytokines implicated in PPROM. Additionally, we have reported that the antioxidant and NFκB inhibitor alpha-lipoic Acid (LA) blocks these TNF-induced effects. We now present the first direct evidence that thrombin also can induce FM weakening in vitro, and LA treatment inhibits this thrombin-induced-weakening. Full thickness FM fragments from unlabored Cesarean deliveries were incubated with increasing doses of thrombin (0-100 u/ml) for 48 h. Fragments were then strength tested (breaking force and work to rupture) using our published methodology. MMP3 and 9 levels in tissue extracts were determined by Western blot and densitometry. To determine the effect of LA, FM fragments were incubated with control medium or 10 u/ml thrombin, with or without 0.25 mM LA. Strength testing and MMP induction were determined. Thrombin induced a dose-dependent decrease in FM strength (42% baseline rupture force and 45% work to rupture) coupled with a dose-dependent increase in MMP3 and 9 expression (all p < 0.001). Treatment of FM with 0.25 mM LA completely inhibited thrombin-induced FM weakening and MMP expression (all p < 0.001). Thrombin treatment of cultured FM induces mechanical weakening and increased MMP3 and 9. Treatment of FM with LA inhibits these thrombin-induced effects. We speculate LA may prove clinically useful in prevention of PPROM associated with abruption.

Changes in cognitive measures associated with a lifestyle program for treated hypertensives: a randomized controlled trial (ADAPT).

Cognitive changes are reported infrequently in programs targeting cardiovascular risk. We examined self-efficacy, behavioral barriers and health beliefs in a lifestyle program for drug-treated hypertensives that aimed to reduce blood pressure, antihypertensive drug needs and cardiovascular risk. In a randomized controlled trial, we compared usual care (controls) and a 4-month program focusing on weight loss, diet and exercise. Outcomes were assessed at baseline, 4 months and 1-year follow-up. Of 241 individuals randomized, 102/123 in the program and 90/118 of controls completed follow-up. In the program group, dietary barriers fell by 14% at 4 months (controls 2%, P = 0.025) and by 8% at follow-up (controls 3%, P = 0.010). Exercise barriers fell by 11% at 4 months (controls 3%, P = 0.020) and 17% (controls 4%, P = 0.002) at follow-up. Dietary self-efficacy improved by 3% at 4 months (controls -1%, P = 0.003) and by 2% at follow-up (controls -1%, P = 0.051). Exercise self-efficacy increased by 8% at 4 months (controls 3%, P < 0.001) and by 5% at follow-up (controls 3%, P = 0.130). Changes in cognitive variables predicted changes in health-related behaviors at 4 months and follow-up. A cognitively based lifestyle program in treated hypertensives is associated with improvements in cognitive measures in the shorter and longer term.

Term human fetal membranes have a weak zone overlying the lower uterine pole and cervix before onset of labor.

The etiology of fetal membrane (FM) rupture is unknown. A hypothesis that the FM weakens by a process of collagen remodeling and apoptosis to facilitate rupture has been proposed. Human FMs reportedly exhibit a zone of altered histology, postulated to be the FM rupture site, but concomitant FM weakness has not been demonstrated. We hypothesized that a discrete zone of FM with marked weakness, histological change, and evidence of remodeling and apoptosis, develops in late gestation in the FM overlying the cervix. FM tissue from women undergoing prelabor cesarean delivery were perioperatively marked to identify the FM overlying the cervix, cut with a procedure that facilitates remapping the rupture strength of FM pieces to their former location and orientation on a three-dimensional model, and tested for strength. A 10-cm FM zone centered at the cervical mark was compared with the remaining FM. Mean rupture strength within the cervical zone was 55% of the remaining FM. The cervical zone also exhibited increased MMP-9 protein, decreased tissue inhibitor of metalloproteinases-3 (TIMP-3) protein, and increased PARP cleavage coincident with the previously reported zone of altered histology. A discrete zone of weakness is present in term prelabor FMs overlying the cervix and has biochemical characteristics consistent with tissue remodeling and apoptosis.

Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro.

Much attention has been given to the influences of bioactive factors on mesenchymal progenitor cell differentiation and proliferation, but few studies have examined the effect of mechanical factors on these cells. This study examined the effects of cyclic hydrostatic pressure on human bone marrow-derived mesenchymal progenitor cells undergoing chondrogenic differentiation. Aggregates of bone marrow-derived mesenchymal progenitor cells were cultured in a defined chondrogenic medium and were subjected to cyclic hydrostatic pressure. Aggregates were loaded at various time points: single (day 1 or 3) or multiple (days 1-7). At 14 and 28 days, aggregates were harvested for histology, immunohistochemistry, and quantitative DNA and matrix macromolecule analysis. The aggregates loaded for a single day did not demonstrate significant changes in proteoglycan and collagen contents compared with the non-loaded controls. In contrast, for the multi-day loaded aggregates, statistically significant increases in proteoglycan and collagen contents were found on both day 14 and day 28. Aggregates loaded for seven days were larger and histological staining indicated a greater matrix/cell ratio. This study indicates that hydrostatic pressure enhances the cartilaginous matrix formation of mesenchymal progenitor cells differentiated in vitro, and suggests that mechanical forces may play an important role in cartilage repair and regeneration in vivo.

Estimation of tendon moment arms from three-dimensional magnetic resonance images.

New three-dimensional (3D) magnetic resonance imaging (MRI) methods for measuring the tendon moment arm were created and were evaluated on the tendon moment arm of the flexor digitorum profundus at the third metacarpophalangeal joint. Using an open magnet MRI system and a hand holder, a series of static images were acquired at four joint angles and analyzed using specially created computer programs. Three methods were evaluated: (1) a 3D tendon excursion method that extended the method of Landsmeer; (2) a 3D geometric method whereby the moment arm was the perpendicular distance between the joint axis of rotation and the tendon path, and (3) a two-dimensional (2D) geometric method whereby single image slices were analyzed. Repeating the imaging and measurement processes, the 3D tendon excursion method was more reproducible (6% variation) than the 3D geometric method (12%), and both were much more reproducible than the 2D geometric method (27%). By having three operators analyze a single set of image data, we found that the precision of the 3D tendon excursion method was much less affected by segmentation error than the 3D geometric method. With the 3D imaging methods, tendon bowstringing and a displacement of the joint center of rotation toward the dorsal side of the hand were evident, leading to as much as a 60% increase in moment arm with joint flexion. Because of the dependence on flexion and variation between subjects, we recommend patient-specific measurements for target applications in functional neuromuscular stimulation interventions and tendon transfer surgery.

Changes in third carpal bone articular cartilage after synovectomy in normal and inflamed joints.

OBJECTIVE: To determine if arthroscopic synovectomy in normal and inflamed joints had temporal or site-related effects on articular cartilage. STUDY DESIGN: Alterations in equine third carpal bone articular cartilage were studied at two time periods: groups 1 and 2 (6 weeks) and groups 3 and 4 (2 weeks) after synovectomy in normal (groups 2 and 4) and inflamed carpi (groups 1 and 3). ANIMAL POPULATION: 16 carpi from eight horses. METHODS: Biochemical and biomechanical properties of dorsal and palmar articular cartilage were determined by radioloabeling, proteoglycan (PG) extraction, chromatography, electrophoresis, and indentation testing. RESULTS: Synovectomy in inflamed joints produced the greatest concentration of newly synthesized PG in articular cartilage by 2 weeks. Synovectomy in normal joints produced significantly greater newly synthesized PG in articular cartilage by 6 weeks. Dorsal sites had greater newly synthesized and endogenous PG in some groups. Chromatographic profiles of newly synthesized PG demonstrated early and late PG peaks. Electrophoresis of late PG peak showed a toluidine blue-positive band that comigrated with human A1D1 PG monomer in the two groups with the most newly synthesized PG> This band was reactive with monoclonal antibody 1C6 specific for the hyaluronic acid-binding region of aggrecan. For the material properties evaluated, only Poisson's ratio was significantly decreased between groups as a function of time (6 weeks < 2 weeks). and this was most pronounced in the thicker dorsal sites. CONCLUSIONS: Synovectomy in inflamed joints produced site-specific, significantly greater responses in articular cartilage as compared with synovectomy in normal joints. CLINICAL RELEVANCE: Synovectomy may not be beneficial to the articular cartilage in inflamed joints.

In vivo kinematics of the rabbit knee in unstable models of osteoarthrosis.

The effects of osteoarthrosis inducing surgery on the kinematics of the rabbit knee were evaluated in vivo. A video motion analysis system was used to track reflective markers attached to two pins fixed in both femur and tibia, and from these data knee kinematics were computed. The control for all measurements was the gait after pins were implanted, but the knee was unaltered. Both a release of the anterior cruciate ligament and a partial medial meniscectomy were then performed, and the animals' gait was recorded at 4, 8 and 12 weeks after knee surgery. Knee kinematics were described by three translations and three rotations and were analyzed in terms of maximum and minimum values and range of motion. Statistical comparisons of these data between control and operated knees were made using Wilcoxon's signed rank test. Results showed an initial increase in maximum anterior displacement which returned to normal after 12 weeks. In addition there was a persistent increase in knee adduction and an increase in the minimum value of external rotation over the 12 week period. At 12 weeks after surgery there was no change in range of any measurable kinematic parameter. Overall, the changes in joint kinematics following partial medial meniscectomy and release of the anterior cruciate ligament were small, suggesting that altered joint kinematics might not be a critical factor in the development of osteoarthrosis in this animal model.

Meniscal transplantation and degenerative articular change: an experimental study in the rabbit.

Over the past several decades, scientific evidence has substantiated the vital role of the meniscus in the function of the knee. Using a modified Mankin method, this study evaluated the efficacy of immediate and delayed meniscal transplantation to prevent the degenerative articular changes seen after medial meniscectomy. Significantly fewer degenerative changes occurred in the articular cartilage from New Zealand white rabbits receiving a meniscal transplantation immediately after meniscectomy when compared with control animals killed 3 months after meniscectomy (P < .05). Rabbits who received a delayed transplantation 3 months after meniscectomy and were killed at 6 months, showed significantly fewer degenerative changes in the articular cartilage compared with control animals killed 6 months (P < .05) or 3 months (P < .05) after meniscectomy. These studies show that both immediate and delayed meniscal allograft transplantation offer some initial protection to the cartilaginous surfaces of the knee following meniscectomy. These studies also suggest that delayed meniscal transplantation may reverse initial postmeniscectomy degenerative changes for the short term.

Some phosphonic acid analogs as inhibitors of pyrophosphate-dependent phosphofructokinase, a novel target in Toxoplasma gondii.

Pyrophosphate-dependent phosphofructokinase (PPi-PFK) was identified previously in Toxoplasma gondii as the only kinase that phosphorylates fructose-6-P to fructose-1,6-bisP. Since such an enzyme is not present in mammals, it was considered to be a good target for prospective selective inhibitors of the parasite. We have examined the effects of several phosphonic acid derivatives, analogs of pyrophosphate, on PPi-PFK activity, as well as on the replication of T. gondii in human foreskin fibroblast (HFF) cells. The most active compound in inhibiting PPi-PFK was tetrasodium carbonyldiphosphonate. Several bisphosphonates and related arylhydrazones showed inhibition of the enzyme, but with higher IC50 values. Although several phosphonoacetic acid derivatives also inhibited PPi-PFK, as a group they were less potent than the bisphosphonate derivatives. Comparison among the structures of various inhibitors and their effects against PPi-PFK indicates that a carbonyl (C=O) or amino (C=N) group between two phosphoryl moieties is associated with more potent enzyme inhibiton. Tetrasodium carbonyldiphosphonate did not show a significant effect against replication of T. gondii cells, probably because, as a charged molecule, it could not cross the cell membrane to reach the intracellular parasite. Tetraisopropyl carbonyldiphosphonate 2,4-dinitrophenylhydrazone showed some selective inhibitory effect against replication of the parasite in the HFF cells and protected the mammalian cells from damage by T. gondii. The results indicate that carbonyldiphosphonic acid is a good prototype compound that is amenable to chemical manipulation, which, in turn, may optimize selective inhibition of T. gondii PPi-PFK and increase accessibility to the intracellular parasite.