Maduramycin, a novel glycosylation modulator for mammalian fed-batch and steady-state perfusion processes.

Controlling high-mannose (HM) content of therapeutic proteins during process intensification, reformulation for subcutaneous delivery, antibody-drug conjugate or biosimilar manufacturing represents an ongoing challenge. Even though a range of glycosylation levers to increase HM content exist, modulators specially increasing M5 glycans are still scarce. Several compounds of the polyether ionophore family were screened for their ability to selectively increase M5 glycans of mAb products and compared to the well-known α-mannosidase I inhibitor kifunensine known to increase mainly M8-M9 glycans.

Generation of site-distinct N-glycan variants for in vitro bioactivity testing.

Glycosylation, a critical product quality attribute, may affect the efficacy and safety of therapeutic proteins in vivo. Chinese hamster ovary fed-batch cell culture batches yielded consistent glycoprofiles of a Fc-fusion antibody comprizing three different N-glycosylation sites. By adding media supplements at specific concentrations in cell culture and applying enzymatic glycoengineering, a diverse N-glycan variant population was generated, including high mannose, afucosylated, fucosylated, agalactosylated, galactosylated, asialylated, and sialylated forms.

Cell culture media supplemented with raffinose reproducibly enhances high mannose glycan formation.

Glycosylation plays a pivotal role in pharmacokinetics and protein physiochemical characteristics. In particular, effector functions including antibody-dependent cell-mediated cytotoxicity (ADCC) can be desired, and it has been described that high-mannose species exhibited enhanced ADCC. In this work we present the trisaccharide raffinose as a novel cell culture medium supplement to promote high mannose N-glycans in fed-batch cultures, which is sought after in the development of biosimilars to match the quality profile of the reference medicinal product (RMP) also.

Osseointegration of dental implants in bone irradiated with 40, 50 or 60 gy doses. An experimental study with beagle dogs.

Construction of different kinds of prostheses on irradiated bone tissues after tumour surgery is a complicated part of modern implantology. In irradiated regions of the jaws where the bone layers are thin and the blood supply also is minimal, knowledge of the impact of each dose of radiation is very important. The aim of this study was to compare the bone response around titanium implants loaded with fixed bridges in dog mandibles irradiated with total doses of 40, 50 or 60 Gy.

Titanium implants and lateral forces. An experimental study with sheep.

The purpose of this study was to investigate the resistance of titanium implants to horizontal forces in a sheep model. Twenty implants were inserted into the foreheads of 5 sheep, 4 implants on each animal. After a healing period of 3 months, abutments were mounted on the implants.

Stability and effect on the soft tissue profile of mandibular setback with sagittal split osteotomy and rigid internal fixation.

The stability and the effect on the soft tissue profile of mandibular setback with sagittal split osteotomy and rigid internal fixation was studied prospectively in 29 consecutive patients, 17 to 55 years old, who had mesial occlusion. Profile cephalometric radiographs were taken immediately before and short after surgery as well as 14 months postsurgically. The mean setback of the mandible 1 to 8 days after surgery was 6.

Revascularized bone grafts for craniofacial reconstruction.

Reconstruction of craniomaxillofacial defects caused by injury, tumor ablation, or congenital deformities can be accomplished by a variety of methods. Nonvascularized (free), vascularized (pedicled), and revascularized (microvascular) bone grafts have been employed for osseous restoration of the upper, mid, and lower facial skeleton. In comprised recipient tissue beds or when rapid functional restoration is desired, revascularized flaps hold certain advantages over their nonrevascularized counterparts.

Stability and effect on the soft tissue profile of mandibular advancement with sagittal split osteotomy and rigid internal fixation.

The stability and the effect on the soft tissue profile of mandibular advancement with sagittal split osteotomy and rigid internal fixation was studied prospectively in 30 consecutive patients, 17 to 32 years old, who had a distal occlusion. Profile roentgen cephalometric recordings were made immediately before and shortly after surgery as well as 13 months postsurgically. The mean advancement of the mandible 3 to 8 days after surgery was 5 mm.

The subcranial approach for fronto-orbital and anteroposterior skull-base tumors.

We describe 78 patients with fronto-orbital and sphenoethmoidal tumors surgically treated with the subcranial approach. This approach was developed by us in 1978 primarily for the treatment of skull-base trauma and craniofacial anomalies. Since 1980, we have extended the indications to include tumor resections.

K+ fluxes mediated by Na(+)-K(+)-Cl- cotransport and Na(+)-K(+)-ATPase pumps in renal tubule cell lines transformed by wild-type and temperature-sensitive strains of Simian virus 40.

The relative contributions of Na(+)-K(+)-ATPase pumps and Na(+)-K(+)-Cl- cotransport to total rubidium (Rb+) influx into primary cultures of renal tubule cells (PC.RC) and cells transformed either with the wild-type or a temperature-sensitive mutant of the simian virus 40 (SV40), were measured under various growth conditions. The Na(+)-K(+)-ATPase-mediated component represented 74% and 44-48% of total Rb+ influx into PC.

Regulation by calcitonin of Na(+)-K(+)-Cl- cotransport in a rabbit thick ascending limb cell line.

The hormonal regulation of a Na(+)-K(+)-Cl- cotransport was investigated in a renal tubule cell line (RC.SV2 cells) transformed by the simian virus 40. This cell line has the main characteristics of cells from the thick ascending limb of Henle, including the presence of Tamm-Horsfall protein and stimulation of adenosine 3',5'-cyclic monophosphate (cAMP) production by calcitonin (CT).

Classification and treatment of zygomatic fractures: a review of 1,025 cases.

The treatment of zygomatic fractures varies among surgeons, and the cosmetic and functional results are frequently less than optimal. A treatment guideline based on a simple classification of zygomatic fractures is presented. The emphasis is placed on the indications for closed and open reduction, consistent methods of three-dimensional alignment and fixation, and the management of concomitant infraorbital rim and orbital floor fractures.

Management of combined frontonaso-orbital/skull base fractures and telecanthus in 355 cases.

In regard to the multiple problems of reconstruction concerning this fracture pattern, we developed various methods to achieve optimal results. As various vital regions, apart from the nasoethmoidal fractures and aesthetics, are involved, the proposed classification has direct implication for the surgical procedure. Even in intracranial fragment dislocations, cerebral contusion, and elevated intracranial pressure, the subcranial approach, in contrast with the transfrontal access, enables early definitive management of the skull base and the external facial frame in a one-stage procedure.

[Hyperbaric oxygen in the treatment of osteoradionecrosis of the mandible].

Osteoradionecrosis (ORN) of the mandible is one of the most dreaded complications in the treatment of cancer of the head and neck. If conservative and surgical treatment have not been successful, very often the only remaining solution is surgical intervention into the bone continuity of the mandible. In a group of eight patients suffering from ORN of the horizontal ramus of the lower jaw we gathered first experiences with hyperbaric oxygen therapy in combination with an operation to preserve the bone continuity (debridement of the bone and closing of the soft tissues).

Treatment of 813 zygoma-lateral orbital complex fractures. New aspects.

A 10-year experience with surgical treatment of 813 zygomalateral orbital complex fractures is reviewed. Regardless of the type or severity of the fracture pattern, concomitant fractures of the orbital floor and rim were approached exclusively through the transconjunctival approach without a lateral canthotomy. The advantages of this approach compared with the subciliary access are the avoidance of a visible scar and markedly reduced incidence of postoperative lower eyelid complications such as ectropion and edema.

Osseo-integration of dental implants in radiated mandibles: an experimental study with beagle dogs.

This investigation was planned to detect the ability of radiated bone to integrate with dental implants and to study the load-bearing capacity of these implants. In five beagle dogs, the premolars were extracted, after which one side of the mandible was radiated with 40 Gy. Three months later, two hollow-cylinder implants were placed on each side of the mandible.

[Lyophilized allogeneic costal cartilage as reconstruction material in middle-ear surgery].

From 1.1. 1983 to 31.

[Primary optic nerve decompression in mid-face fractures].

In severe craniofacial-frontobasal injuries the optic nerve is quite often damaged. We report the findings and the visual outcome in 21 patients with severe mid-face fractures, who underwent primary optic nerve decompression after showing an afferent pupillary defect. During the subcranial exploration and the optic nerve decompression, fractures of the optic canal were found in 13 cases; a dislocated bone fragment could be removed in 6 patients.

Subcranial approach for the correction of hypertelorism.

The subcranial approach for the osteotomy of the skull base and orbital roof in cases with hypertelorism is described. Advancement of the fronto-orbital segments is performed, avoiding the transfrontal procedure, thus making frontal lobe retraction unnecessary. The advantages of this method are pointed out.

[Mandibular reconstruction with the titanium-hollow screw-reconstruction plate system (THORP)].

The THORP system is designed for bridging mandibular defects and for internal osteosynthesis of mandibular fractures. The major aspects and advantages of the THORP system compared with the conventional reconstruction plates and screws are: 1. The rigid fixation of the head of the screw to the plate, thus avoiding unphysiological loads to the bone underneath the plate.

[The correction of craniofacial deformities].

Subject of this paper is to emphasize the advantages of our surgical procedure for the correction of craniofacial anomalies. Particularly for the fronto-orbital advancement in the hypertelorism and exophthalmus cases, this method enabled the reduction of the complication rate and the preservation of vital structures as well as a significant reduction of the morbidity rate. The advantages rendered by the bimaxillary osteotomy are discussed.